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Modifier Selection by Transgenes: The Case of Growth Hormone Transgenesis and Hyperactive Circling Mice

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Abstract

Deleterious impacts of major mutations can be ameliorated by stabilising selection acting on modifier genes. We hypothesise that a new hyperactive circling mouse (counterspin: Cr) arises when modifier genes inadvertently selected to ameliorate the negative impacts of a growth hormone transgenic insertion segregate into the normal genetic background that lacks the transgene. We hypothesise that such modifiers generate a phenotype “mirror image” to the transgenics on the otherwise normal background. We highlight this by testing a priori hypotheses that counterspin and transgenic growth hormone mice deviate oppositely from normal mice across a broad spectrum of characteristics. Results spanning growth, sensorimotor performance, cognition and striatal neurotransmitters provide strong circumstantial evidence for the hypothesis. In a more direct test for selection in the transgenic mice, we found that those examined in 2008 slept ~3 h/d less than they did 14 years ago (P < 0.0005). This is a profound change strongly supporting the reality of modifier selection in these mice. Our results highlight that modifiers may act powerfully on genetically engineered constructs given a genetically variable background. Furthermore, we suggest that modifier selection might provide a novel method for deriving genetic models, and specifically, models phenotypically opposite to engineered constructs or natural mutations.

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References

  • Anisman, H., Hayley, S., Kelly, O., Borowski, T., & Merali, Z. (2001). Psychogenic, neurogenic, and systemic stressor effects on plasma corticosterone and behavior: Mouse strain-dependent outcomes. Behavioral Neuroscience, 115, 443–454. doi:10.1037/0735-7044.115.2.443.

    PubMed  CAS  Google Scholar 

  • Aspide, R., Carnevale, U. A. G., Sergeant, J. A., & Sadile, A. G. (1998). Non-selective attention and nitric oxide in putative animal models of Attention-Deficit Hyperactivity Disorder. Behavioural Brain Research, 95, 123–133. doi:10.1016/S0166-4328(97)00217-9.

    PubMed  CAS  Google Scholar 

  • Baldwin, J. M. (1902). Development and evolution. New York: MacMillan & Co.

    Google Scholar 

  • Bao, L., Avshalumov, M. V., & Rice, M. E. (2005). Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, but not ATP depletion. The Journal of Neuroscience, 25, 10029–10040. doi:10.1523/JNEUROSCI.2652-05.2005.

    PubMed  CAS  Google Scholar 

  • Barsh, G. S., & Schwartz, M. W. (2002). Genetic approaches to studying energy balance: Perception and integration. National Review, 3, 589–600. doi:10.1038/nrn902.

    CAS  Google Scholar 

  • Bartke, A. (2003). Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice. Neuroendocrinology, 78, 210–216. doi:10.1159/000073704.

    PubMed  CAS  Google Scholar 

  • Bartke, A., Cecim, M., Tang, K., Steger, A. W., Chandrashekar, V., & Turyn, D. (1994). Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice. Experimental Biology and Medicine, 206, 345–357.

    CAS  Google Scholar 

  • Bartke, A., Chandrashekar, V., Turyn, T., Steger, R. W., Debeljuk, L., Winters, T. A., et al. (1999). Minireview: Effects of growth hormone overexpression and growth hormone resistance on neuroendocrine and reproductive functions in transgenic and knock-out mice. Experimental Biology and Medicine, 222, 113–123. doi:10.1046/j.1525-1373.1999.d01-121.x.

    CAS  Google Scholar 

  • Belforte, J. E., Magarinos-Azcone, C., Armando, I., Buno, W., & Pazo, J. H. (2001). Pharmacological involvement of the calcium blocker flunarizine in dopamine transmission at the striatum. Parkinsonism & Related Disorders, 8, 33–40. doi:10.1016/S1353-8020(01)00006-2.

    CAS  Google Scholar 

  • Belforte, J. E., & Pazo, J. H. (2004). Turning behaviour induced by stimulation of the 5-HT receptors in the subthalamic nucleus. The European Journal of Neuroscience, 19, 346–355. doi:10.1111/j.0953-816X.2003.03125.x.

    PubMed  CAS  Google Scholar 

  • Blackburn, T. P., Kemp, J. D., Martin, D. A., & Cox, B. (1984). Evidence that 5-HT agonist-induced rotational behaviour in the rat is mediated via 5-HT1 receptors. Psychopharmacology, 83, 163–165. doi:10.1007/BF00429727.

    PubMed  CAS  Google Scholar 

  • Blaszczyk, J. W. (2003). Startle response to short acoustic stimuli in rats. Acta Neurobiologiae Experimentalis, 63, 25–30.

    PubMed  Google Scholar 

  • Bohlooly, Y. M., Olsson, B., Gritli-Linde, A., Brusehed, O., Isaksson, O. G. P., Ohlsson, C., et al. (2001). Enhanced spontaneous locomotor activity in bovine GH transgenic mice involves peripheral mechanisms. Endocrinology, 142, 4560–4567. doi:10.1210/en.142.10.4560.

    Google Scholar 

  • Bothe, G. W. M., Bolivar, V. J., Vedder, M. J., & Geistfeld, J. G. (2005). Behavioral differences among fourteen inbred mouse strains commonly used as disease models. Comparative Medicine, 55, 326–334.

    PubMed  CAS  Google Scholar 

  • Brown-Borg, H. M., Johnson, W. T., Rakoczy, S., & Romanick, M. (2001). Mitochondrial oxidant generation and oxidative stress in Ames dwarf and GH transgenic mice. Journal of the American Aging Association, 24, 85–100.

    CAS  Google Scholar 

  • Cammalleri, M., Cervia, D., Monte, M. D., Martini, D., Langenegger, D., Fehlmann, D., et al. (2006). Compensatory changes in the hippocampus of somatostatin knockout mice: Upregulation of somatostatin receptor 2 and its function in the control of bursting activity and synaptic transmission. The European Journal of Neuroscience, 23, 2404–2422. doi:10.1111/j.1460-9568.2006.04770.x.

    PubMed  Google Scholar 

  • Cecim, M., Alvarez-Sanz, M., Van de Kar, L., Milton, S., & Bartke, A. (1996). Increased plasma corticosterone levels in bovine growth hormone (bGH) transgenic mice: Effects of ACTH, GH and IGF-I on in vitro adrenal corticosterone production. Transgenic Research, 5, 187–192. doi:10.1007/BF01969708.

    PubMed  CAS  Google Scholar 

  • Chartoff, E. H., Marck, B. T., Matsumoto, A. M., Dorsa, D. M., & Palmiter, R. D. (2001). Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor activation. Proceedings of the National Academy of Sciences of the United States of America, 98, 10451–10456. doi:10.1073/pnas.181356498.

    PubMed  CAS  Google Scholar 

  • Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., et al. (2005). Reduced sleep in Drosophila Shaker mutants. Nature, 434, 1087–1092. doi:10.1038/nature03486.

    PubMed  CAS  Google Scholar 

  • Clark, R. E., Zola, S. M., & Squire, L. R. (2000). Impaired recognition memory in rats after damage to the hippocampus. The Journal of Neuroscience, 20, 8853–8860.

    PubMed  CAS  Google Scholar 

  • Collin, G. B., Maddatu, T. P., Sen, S., & Naggert, J. K. (2005). Genetic modifiers interact with Cpefat to affect body weight, adiposity, and hyperglycemia. Physiological Genomics, 22, 182–190. doi:10.1152/physiolgenomics.00208.2003.

    PubMed  CAS  Google Scholar 

  • Cools, A. R. (1972). Neurochemical correlates of the Waltzing-Shaker syndrome in thevariant-Waddler mouse. Psychopharmalogia, 24, 384–396. doi:10.1007/BF00402533.

    CAS  Google Scholar 

  • Crenshaw, E. B., III, Ryan, A., Dillon, S. R., Kalla, K., & Rosenfeld, M. G. (1991). Wocko, a neurological mutant generated in a transgenic mouse pedigree. The Journal of Neuroscience, 11, 1524–1530.

    PubMed  Google Scholar 

  • Crespi, F. (1993). Functional in vivo interaction between growth hormone and dopamine systems are correlated to changes in striatal somatostatin levels as determined by voltammetry. Experimental Brain Research, 94, 363–370. doi:10.1007/BF00230196.

    CAS  Google Scholar 

  • Cryns, K., Van Alphen, A. M., Van Spaendonck, M. P., Van de Heyning, P. H., Timmermans, J. P., De Zeeuw, C. I., et al. (2004). Circling behavior in the Ecl mouse is caused by lateral semicircular canal defects. The Journal of Comparative Neurology, 468, 587–595. doi:10.1002/cne.10975.

    PubMed  Google Scholar 

  • Cryns, K., Van Spaendonck, M. P., Flothmann, K., van Alphen, A. M., Van De Heyning, P. H., Timmermans, J. P., et al. (2002). Vestibular dysfunction in the epistatic circler mouse is caused by phenotypic interaction of one recessive gene and three modifier genes. Genome Research, 12, 613–617. doi:10.1101/gr.218402.

    PubMed  CAS  Google Scholar 

  • Cutting, G. R. (2005). Modifier genetics: Cyctic fibrosis. Annual Review of Genomics and Human Genetics, 6, 237–260. doi:10.1146/annurev.genom.6.080604.162254.

    PubMed  CAS  Google Scholar 

  • Denenberg, V. H., Kim, D. S., & Palmiter, R. D. (2004). The role of dopamine in learning, memory, and performance of a water escape task. Behavioural Brain Research, 148, 173–178. doi:10.1016/S0166-4328(03)00183-9.

    Google Scholar 

  • Deschaux, O., Bizot, J. C., & Goyffon, M. (1997). Apamin improves learning in an object recognition task in rats. Neuroscience Letters, 222, 159–162. doi:10.1016/S0304-3940(97)13367-5.

    PubMed  CAS  Google Scholar 

  • Donahue, C. P., Kosik, K. S., & Shors, T. J. (2006). Growth hormone is produced within the hippocampus where it responds to age, sex and stress. Proceedings of the National Academy of Sciences of the United States of America, 103, 6031–6036. doi:10.1073/pnas.0507776103.

    PubMed  CAS  Google Scholar 

  • Doolittle, D. P. (1963). Two-gene circling in the mouse. Genetics, 48, 887.

    Google Scholar 

  • Douglas, C. L., Vyazovskiy, V., Southard, T., Chiu, S. Y., Messing, A., Tonnoni, G., et al. (2007). Sleep in Kcna2 knockout mice. BMC Biology, 5, 42. doi:10.1186/1741-7007-5-42.

    PubMed  Google Scholar 

  • Espino, A., Calopa, M., Ambrosio, S., Ortola, J., Peres, J., & Navarro, M. A. (1995). CSF somatostatin increase in patients with early parkinsonian syndrome. Journal of Neural Transmission, 9, 189–196. doi:10.1007/BF02259660.

    PubMed  CAS  Google Scholar 

  • Espinosa, F., Marks, G., Heintz, N., & Joho, R. H. (2004). Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels. Genes Brain & Behavior, 3, 90–100. doi:10.1046/j.1601-183x.2003.00054.x.

    CAS  Google Scholar 

  • Fadel, J., & Deutch, A. Y. (2002). Anatomical substrates of orexin–dopamine interactions: Lateral hypothalamic projections to the ventral tegmental area. Neuroscience, 111, 379–387. doi:10.1016/S0306-4522(02)00017-9.

    PubMed  CAS  Google Scholar 

  • Fedrowitz, M., Potschka, H., Richter, A., & Loscher, W. (2000). A microdialysis study of striatal dopamine release in the circling rat, a genetic animal model with spontaneous lateralized rotational behavior. Neuroscience, 97, 69–77. doi:10.1016/S0306-4522(00)00040-3.

    PubMed  CAS  Google Scholar 

  • Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M., & Tsai, L. H. (2007). Recovery of learning and memory is associated with chromatin remodelling. Nature, 447, 178–183. doi:10.1038/nature05772.

    PubMed  CAS  Google Scholar 

  • Fitzgerald, L. W., Miller, K. L., Ratty, A. K., Glick, S. D., Teitler, M., & Gross, K. W. (1992). Asymmetric elevation of striatal dopamine D2 receptors in the chakragati mouse: Neurobehavioral dysfunction in a trangenic insertional mutant. Brain Research, 580, 18–26. doi:10.1016/0006-8993(92)90922-V.

    PubMed  CAS  Google Scholar 

  • Fitzgerald, L. W., Ratty, A. K., Teitler, M., Gross, K. W., & Glick, S. D. (1993). Specificity of behavioral and neurochemical dysfunction in the chakragati mouse: A novel genetic model of a movement disorder. Brain Research, 608, 247–258. doi:10.1016/0006-8993(93)91465-5.

    PubMed  CAS  Google Scholar 

  • Gainetdinov, R. R., Wetsel, W. C., Jones, S. R., Levin, E. D., Jaber, M., & Caron, M. G. (1999). Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science, 283, 397–401. doi:10.1126/science.283.5400.397.

    PubMed  CAS  Google Scholar 

  • Gerlai, R. (1996). Gene-targeting studies of mammalian behavior: Is it the mutation or the background genotype? Trends in Neurosciences, 19, 177–181. doi:10.1016/S0166-2236(96)20020-7.

    PubMed  CAS  Google Scholar 

  • Ghelardini, C., Quattrone, A., Galeotti, N., Livi, S., Banchelli, G., Raimondi, L., et al. (2003). Antisense knockdown of the Shaker-like Kv1.1 gene abolishes the central stimulatory effects of amphetamines in mice and rats. Neuropsychopharmacology, 28, 1096–1105.

    PubMed  CAS  Google Scholar 

  • Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature, 379, 606–612. doi:10.1038/379606a0.

    PubMed  CAS  Google Scholar 

  • Glick, S. D., & Carlson, J. N. (1989). Regional changes in brain dopamine and serotonin metabolism induced by conditioned circling in rats: Effects of water deprivation, learning and individual differences in asymmetry. Brain Research, 504, 231–237. doi:10.1016/0006-8993(89)91362-0.

    PubMed  CAS  Google Scholar 

  • Grammatikopoulos, G., Pignatelli, M., D’Amico, F., Fiorillo, C., Fresiello, A., & Sadie, A. G. (2002). Selective inhibition of neuronal nitric oxide synthesis reduces hyperactivity and increases non-selective attention in the Naples High-Excitability rat. Behavioural Brain Research, 130, 127–132. doi:10.1016/S0166-4328(01)00424-7.

    PubMed  CAS  Google Scholar 

  • Hajdu, I., Obal, F., Jr, Fang, J., Krueger, J. M., & Rollo, C. D. (2002). Sleep of transgenic mice producing excess rat growth hormone. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 282, R70–R76.

    PubMed  CAS  Google Scholar 

  • Hathway, G. J., Humphrey, P. P. A., & Kendrick, K. M. (2003). Somatostatin induces striatal dopamine release and contralateral turning behaviour in the mouse. Neuroscience Letters, 358, 127–131. doi:10.1016/j.neulet.2003.09.056.

    Google Scholar 

  • Hess, E. J., Collins, K. A., & Wilson, M. C. (1996). Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. The Journal of Neuroscience, 16, 3104–3111.

    PubMed  CAS  Google Scholar 

  • Hickman-Davis, J. M. (2001). Implications of mouse genotype for phenotype. News in Physiological Sciences, 16, 19–22.

    PubMed  CAS  Google Scholar 

  • Hurley, D. L., Birch, D. V., Almond, M. C., Estrada, I. J., & Phelps, C. J. (2003). Reduced hypothalamic neuropeptide Y expression in growth hormone- and prolactin-deficient Ames and Snell dwarf mice. Endocrinology, 144, 4783–4789. doi:10.1210/en.2003-0753.

    PubMed  CAS  Google Scholar 

  • Isaac, S. O., & Berridge, C. W. (2003). Wake-promoting actions of dopamine D1 and D2 receptor stimulation. The Journal of Pharmacology and Experimental Therapeutics, 307, 386–394. doi:10.1124/jpet.103.053918.

    PubMed  CAS  Google Scholar 

  • Ishikawa, Y., Shimatsu, A., Murakami, Y., & Imura, H. (1990). Barrel rotation in rats induced by SMS 201-995: Suppression by ceruletide. Pharmacology, Biochemistry and Behavior, 37, 523–526. doi:10.1016/0091-3057(90)90022-A.

    CAS  Google Scholar 

  • Jenner, P. (2003). Oxidative stress in Parkinson’s disease. Annals of Neurology, 53(Suppl. 3), S26–S38. doi:10.1002/ana.10483.

    PubMed  CAS  Google Scholar 

  • Jinnah, H. A., Jones, M. D., Wojcik, B. E., Rothstein, J. D., Hess, E. J., Friedmann, T., et al. (1999). Influence of strain and age on striatal dopamine loss in a genetic mouse model of Lesch-Nyhan disease. Journal of Neurochemistry, 72, 225–229. doi:10.1046/j.1471-4159.1999.0720225.x.

    PubMed  CAS  Google Scholar 

  • Johansson, J. O., Larsson, G., Andesson, M., Elmgren, A., Hynsjo, L., Lindahl, A., et al. (1995). Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters. Neuroendocrinology, 61, 57–66. doi:10.1159/000126813.

    PubMed  CAS  Google Scholar 

  • Joho, R. H., Street, C., Matsushita, S., & Knopfel, T. (2005). Behavioural motor dysfunction in Kv3-type potassium channel-deficient mice. Genes Brain & Behavior, 5, 472–482. doi:10.1111/j.1601-183X.2005.00184.x.

    Google Scholar 

  • Kaiser, A., Fedrowitz, M., Ebert, U., Zimmermann, E., Hedrich, H. J., Wedekind, D., et al. (2001). Auditory and vestibular defects in the circling (ci2) rat mutant. The European Journal of Neuroscience, 14, 1129–1142. doi:10.1046/j.0953-816x.2001.01726.x.

    PubMed  CAS  Google Scholar 

  • Kajiura, L. J., & Rollo, C. D. (1996). The ontogeny of resource allocation in giant transgenic rat growth hormone mice. Canadian Journal of Zoology, 74, 492–507. doi:10.1139/z96-058.

    Google Scholar 

  • Kamsler, A., & Segal, M. (2003). Hydrogen peroxide modulation of synaptic plasticity. The Journal of Neuroscience, 23, 269–276.

    PubMed  CAS  Google Scholar 

  • Keithahn, C., & Lerchi, A. (2005). 5-Hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C. Journal of Pineal Research, 38, 62–66. doi:10.1111/j.1600-079X.2004.00177.x.

    PubMed  CAS  Google Scholar 

  • Kiernan, A. E., Erven, A., Voegeling, S., Peters, J., Nolan, P., Hunter, J., et al. (2002). ENU mutagenesis reveals a highly mutable locus on mouse chromosome 4 that affects ear morphogenesis. Mammalian Genome, 13, 142–148.

    Article  PubMed  CAS  Google Scholar 

  • Kikkawa, Y., Shitara, H., Wakana, S., Kohara, Y., Takada, T., Okamoto, M., et al. (2003). Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice. Human Molecular Genetics, 12, 453–461. doi:10.1093/hmg/ddg042.

    PubMed  CAS  Google Scholar 

  • Kim, M. J., Shin, K. S., Chung, Y. B., Jung, K. W., Cha, C. I., & Shin, D. H. (2005). Immunohistochemical study of p47Phox and gp91Phox distributions in rat brain. Brain Research, 1040, 178–186. doi:10.1016/j.brainres.2005.01.066.

    PubMed  CAS  Google Scholar 

  • Kincaid, A. E. (2001). Spontaneous circling behavior and dopamine neuron loss in a genetically hypothyroid mouse. Neuroscience, 105, 891–898. doi:10.1016/S0306-4522(01)00229-9.

    PubMed  CAS  Google Scholar 

  • Kiss, J. P., & Vizi, E. S. (2001). Nitric oxide: A novel link between synaptic and nonsynaptic transmission. Trends in Neurosciences, 24, 211–215. doi:10.1016/S0166-2236(00)01745-8.

    PubMed  CAS  Google Scholar 

  • Kitami, T., & Nadeau, J. H. (2002). Biochemical networking contributes more to genetic buffering in human and mouse metabolic pathways than does gene duplication. Nature Genetics, 32, 191–194. doi:10.1038/ng945.

    PubMed  CAS  Google Scholar 

  • Koni, P. A., Khanna, R., Chang, M. C., Tang, M. D., Kaczmarek, L. K., Schlichter, L. C., et al. (2003). Compensatory anion currents in Kv1.3 channel-deficient thymocytes. The Journal of Biological Chemistry, 278, 39443–39451. doi:10.1074/jbc.M304879200.

    PubMed  CAS  Google Scholar 

  • Koshikawa, N., Mori, E., Maruyama, Y., Yatsushige, N., & Kobayashi, M. (1990). Role of dopamine D-1 and D-2 receptors in the ventral striatum in the turning behaviour of rats. European Journal of Pharmacology, 178, 233–237. doi:10.1016/0014-2999(90)90480-T.

    PubMed  CAS  Google Scholar 

  • Kourie, J. I. (1998). Interaction of reactive oxygen species with ion transport mechanisms. American Journal of Physiology. Cell Physiology, 275, C1–C24.

    CAS  Google Scholar 

  • Koutsilieri, E., Scheller, C., Grunblatt, E., Nara, K., Li, J., & Riederer, P. (2002). Free radicals in Parkinson’s disease. Journal of Neurology, 249(Suppl. 2), II1–II5. doi:10.1007/s00415-002-1201-7.

    PubMed  Google Scholar 

  • Kumar, A., Choi, H. K., Renthal, W., Tsankova, N. M., Theobald, D. E. H., Truong, H. T., et al. (2005). Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron, 48, 303–314. doi:10.1016/j.neuron.2005.09.023.

    PubMed  CAS  Google Scholar 

  • Kume, K., Kume, S., Park, S. K., Hirsh, J., & Jackson, F. R. (2005). Dopamine is a regulator of arousal in the fruit fly. The Journal of Neuroscience, 25, 7377–7384. doi:10.1523/JNEUROSCI.2048-05.2005.

    PubMed  CAS  Google Scholar 

  • Lachmansingh, E., & Rollo, C. D. (1994). Evidence for a trade-off between growth and behavioural activity in giant ‘Supermice’ genetically engineered with extra growth hormone genes. Canadian Journal of Zoology, 72, 2158–2168. doi:10.1139/z94-288.

    Google Scholar 

  • Lagziel, A., Ahmed, Z. M., Schultz, J. M., Morell, R. J., Belyantseva, I. A., & Friedman, T. B. (2005). Spatiotemporal pattern and isoform of cadherin 23 in wild type and waltzer mice during inner ear hair cell development. Developmental Biology, 280, 295–306. doi:10.1016/j.ydbio.2005.01.015.

    PubMed  CAS  Google Scholar 

  • Lemon, J. A., Boreham, D. R., & Rollo, C. D. (2003). A dietary supplement abolishes age-related cognitive decline in transgenic mice expressing elevated free radical processes. Experimental Biology and Medicine, 228, 800–810.

    PubMed  CAS  Google Scholar 

  • Lemon, J. A., Boreham, D. R., & Rollo, C. D. (2005). A complex dietary supplement extends longevity of mice. Journal of Gerontology, 60A, 275–279.

    CAS  Google Scholar 

  • Lemon, J. A., Rollo, C. D., & Boreham, D. R. (2008b). Elevated DNA damage in a mouse model of oxidative stress: Impacts of ionizing radiation and a protective dietary supplement. Mutagenesis. doi:10.1093/mutage/gen036.

  • Lemon, J. A., Rollo, C. D., McFarlane, N. M., & Boreham, D. R. (2008a). Radiation-induced apoptosis in mouse lymphocytes is modified by a complex dietary supplement: The effect of genotype and gender. Mutagenesis. doi:10.1093/mutage/gen038.

  • Lessenich, A., Lindemann, S., Richter, A., Hedrich, H. J., Wedekind, D., Kaiser, A., et al. (2001). A novel black-hooded mutant rat (ci3) with spontaneous circling behavior but normal auditory and vestibular functions. Neuroscience, 107, 615–628. doi:10.1016/S0306-4522(01)00390-6.

    PubMed  CAS  Google Scholar 

  • Letts, V. A., Valenzuela, A., Dunbar, C., Zheng, Q. Y., Johnson, K. R., & Frankel, W. N. (2000). A new spontaneous mouse mutation in the Kcne1 gene. Mammalian Genome, 11, 831–835. doi:10.1007/s003350010178.

    PubMed  CAS  Google Scholar 

  • Li, Y., Kelder, B., & Kopchick, J. J. (2001). Identification, isolation, and cloning of growth hormone (GH)-inducible interscapular brown adipose complementary deoyribonuclcleic acid from GH antagonist mice. Endocrinology, 142, 2937–2945. doi:10.1210/en.142.7.2937.

    PubMed  CAS  Google Scholar 

  • Luo, Y., & Roth, G. S. (2000). The roles of dopamine oxidative stress and dopamine receptor signaling in aging and age-related neurodegeneration. Antioxidants & Redox Signalling, 2, 449–460. doi:10.1089/15230860050192224.

    CAS  Google Scholar 

  • Mahmoud, G. S., & Grover, L. M. (2006). Growth hormone enhances excitatory synaptic transmission in area CA1 of rat hippocampus. Journal of Neurophysiology, 95, 2962–2974. doi:10.1152/jn.00947.2005.

    PubMed  CAS  Google Scholar 

  • Meis, S., Sosulina, L., Schulz, S., Hollt, V., & Pape, H. C. (2005). Mechanisms of somatostatin-evoked responses in neurons of the rat lateral amygdala. The European Journal of Neuroscience, 21, 755–762. doi:10.1111/j.1460-9568.2005.03922.x.

    PubMed  Google Scholar 

  • Meliska, C. J., Bartke, A., Vandergriff, J. L., & Jensen, R. A. (1995). Ethanol and nicotine consumption and preference in transgenic mice overexpressing bovine growth hormone gene. Pharmacology, Biochemistry and Behavior, 50, 563–570. doi:10.1016/0091-3057(94)00345-9.

    CAS  Google Scholar 

  • Meng, W., Tobin, J. R., & Busija, D. W. (1995). Glutamate-induced cerebral vasodilation is mediated by nitric oxide through N-methyl-d-aspartate receptors. Stroke, 26, 857–863.

    PubMed  CAS  Google Scholar 

  • Michel, P. P., Ruberg, M., & Hirsch, E. (2006). Dopaminergic neurons reduced to silence by oxidative stress: An early step in the death cascade in Parkinson’s disease? Science STKE, 332, pe19. doi:10.1126/stke.3322006pe19.

  • Mollace, V., Iannone, M., Muscoli, C., Palma, E., Granato, T., Rispoli, V., et al. (2003). The role of oxidative stress in paraquat-induced neurotoxicity in rats: Protection by non peptidyl superoxide dismutase mimetic. Neuroscience Letter, 335, 163–166.

    CAS  Google Scholar 

  • Nadeau, J. H. (2001). Modifier genes in mice and humans. Nature Reviews. Genetics, 2, 165–174. doi:10.1038/35056009.

    PubMed  CAS  Google Scholar 

  • Nadeau, J. H. (2003a). Modifier genes and protective alleles in humans and mice. Current Opinion in Genetics and Development, 13, 290–295. doi:10.1016/S0959-437X(03)00061-3.

    PubMed  CAS  Google Scholar 

  • Nadeau, J. H. (2003b). Modifying the message. Science, 301, 927–928. doi:10.1126/science.1088948.

    PubMed  CAS  Google Scholar 

  • Nadeau, J. H. (2005). Listening to genetic background noise. The New England Journal of Medicine, 353, 1598–1599. doi:10.1056/NEJMe058054.

    Google Scholar 

  • Nakamura, T., Uramura, K., Nambu, T., Yada, T., Goto, K., Yanagisawa, M., et al. (2000). Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic system. Brain Research, 873, 181–187. doi:10.1016/S0006-8993(00)02555-5.

    PubMed  CAS  Google Scholar 

  • Narita, M., Nagumo, Y., Hashimoto, S., Narita, M., Khotib, J., Miyatake, M., et al. (2006). Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviours induced by morphine. The Journal of Neuroscience, 26, 398–405. doi:10.1523/JNEUROSCI.2761-05.2006.

    PubMed  CAS  Google Scholar 

  • Noh, K. M., & Koh, J. Y. (2000). Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. The Journal of Neuroscience, 20, 111–116.

    Google Scholar 

  • Nolan, P. M., Sollars, P. J., Bohne, B. A., Ewens, W. J., Pickard, G. E., & Bucan, M. (1995). Heterozygosity mapping of partially congenic lines: Mapping of a semidominant neurological mutation, Wheels (Whl), on mouse chromosome 4. Genetics, 140, 245–254.

    PubMed  CAS  Google Scholar 

  • Palmiter, R. D., Brinster, R. L., & Hammer, R. E. (1982). Dramatic growth of mice that develop from eggs microinjected with metallothionien-growth hormone fusion genes. Nature, 300, 611–615. doi:10.1038/300611a0.

    PubMed  CAS  Google Scholar 

  • Pan, W., Yu, Y., Cain, C. C., Nyberg, F., Couraud, P. O., & Kastin, A. J. (2005). Permeation of growth hormone across the blood–brain barrier. Endocrinology, 146, 4898–4904. doi:10.1210/en.2005-0587.

    PubMed  CAS  Google Scholar 

  • Pardo, L. A. (2004). Voltage-gated potassium channels in cell proliferation. Physiology (Bethesda, MD), 19, 285–292. doi:10.1152/physiol.00011.2004.

    CAS  Google Scholar 

  • Perreault, M. L., & Rollo, C. D. (2004). Transgenic growth hormone mice exposed to lifetime constant illumination: Gender-specific effects. Canadian Journal of Zoology, 82, 950–965. doi:10.1139/z04-071.

    CAS  Google Scholar 

  • Pigliucci, M., & Preston, K. (Eds.). (2004). Phenotypic integration: Studying the ecology and evolution of complex phenotypes. New York: Oxford University Press.

    Google Scholar 

  • Prisino, R., Galeotti, N., Livi, S., Raimondi, L., & Ghelardini, C. (2006). 4-Methyl benzylamine stimulates food consumption and counteracts the hypophagic effects of amphetamine acting on brain Shaker-like Kv1.1 channels. British Journal of Pharmacology, 147, 218–224. doi:10.1038/sj.bjp.0706465.

    Google Scholar 

  • Propst, F., Rosenberg, M. P., Cork, L. C., Kovatch, R. M., Rauch, S., Westphal, H., et al. (1990). Neuropathological changes in transgenic mice carrying copies of a transcriptionally activated Mos protooncogene. Proceedings of the National Academy of Sciences of the United States of America, 87, 9703–9707. doi:10.1073/pnas.87.24.9703.

    PubMed  CAS  Google Scholar 

  • Qui, J., Ogus, S., Mounzih, K., Ewart-Toland, A., & Chehab, F. F. (2001). Leptin-deficient mice backcrossed to the BALB/cJ genetic background have reduced adiposity, enhanced fertility, normal body temperature, and severe diabetes. Endocrinology, 142, 3421–3425. doi:10.1210/en.142.8.3421.

    Google Scholar 

  • Quist, J. F., Barr, C. L., Schachar, R., Roberts, W., Malone, M., Tannock, R., et al. (2003). The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder. Molecular Psychiatry, 8, 98–102.

    PubMed  CAS  Google Scholar 

  • Raimondi, L., Alfarano, C., Pacini, A., Livi, S., Ghelarardini, C., DeSiena, G., et al. (2007). Methylamine-dependent release of nitric oxide and dopamine in the CNS modulates food intake in fasting rats. British Journal of Pharmacology, 150, 1003–1010. doi:10.1038/sj.bjp.0707170.

    PubMed  CAS  Google Scholar 

  • Ratty, A. K., Matsuda, Y., Elliott, R. W., Chapman, V. M., & Gross, K. W. (1992). Genetic mapping of two DNA markers, D16Ros1 and D16Ros2: Flanking the mutation site in the chakragati mouse, a transgenic insertional mutant. Mammalian Genome, 3, 5–10. doi:10.1007/BF00355834.

    PubMed  CAS  Google Scholar 

  • Reddy, P. H., Vinod, C., Williams, M., Miller, G., Whhetsel, W. O., Jr, & Tagle, D. A. (1999). Transgenic mice expressing mutated full-length HD cDNA: A paradigm for locomotor changes and selective neuronal loss in Huntington’s disease. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 354, 1035–1045. doi:10.1098/rstb.1999.0456.

    PubMed  CAS  Google Scholar 

  • Richards, J. B., Sabol, K. E., & Freed, C. R. (1990). Conditioned rotation: A behavioral analysis. Physiology & Behavior, 47, 1083–1087. doi:10.1016/0031-9384(90)90356-9.

    CAS  Google Scholar 

  • Rollo, C. D. (1994). Phenotypes: Their epigenetics, ecology and evolution. London: Chapman and Hall.

    Google Scholar 

  • Rollo, C. D. (2002). Growth negatively impacts the life span of mammals. Evolution & Development, 4, 55–61. doi:10.1046/j.1525-142x.2002.01053.x.

    Google Scholar 

  • Rollo, C. D. (2004). Life = Epigenetics, ecology and evolution (L = E3): A review of developmental plasticity and evolution, by Mary Jane West-Eberhard. Evolution & Development, 6, 58–62. doi:10.1111/j.1525-142X.2004.04006.x.

    Google Scholar 

  • Rollo, C. D. (2005). Review of “Phenotypic integration: Studying the ecology and evolution of complex phenotypes”. In M. Pigliucci & K. Preston (Eds.), Oxford University Press. Quarterly Review of Biology, 80, 112–113.

  • Rollo, C. D. (2006). Radiation and the regulatory landscape of neo2-Darwinism. Mutation Research, 597, 18–31. doi:10.1016/j.mrfmmm.2005.09.009.

    PubMed  CAS  Google Scholar 

  • Rollo, C. D. (2007a). Overview of research on giant transgenic mice with emphasis on the brain and aging. In T. Samaras (Ed.), Human body size and the laws of scaling (pp. 235–260). New York: Nova Biomedical Publishers.

    Google Scholar 

  • Rollo, C. D. (2007b). Technical review of molecular and physiological aspects relevant to size, free radicals and aging. In T. Samaras (Ed.), Human body size and the laws of scaling (pp. 341–357). New York: Nova Biomedical Publishers.

    Google Scholar 

  • Rollo, C. D. (2007c). Multidisciplinary aspects of regulatory systems relevant to multiple stressors: Aging, xenobiotics and radiation. In C. Mothersill, I. Mosse & S. Seymour (Eds.), Multiple stressors: A challenge for the future (pp. 185–224). New York: Springer.

    Google Scholar 

  • Rollo, C. D. (2008). Dopamine and aging: Intersecting facets. Neurochemical Research (in press).

  • Rollo, C. D., Carlson, J., & Sawada, M. (1996). Accelerated aging of giant transgenic mice is associated with elevated free radical processes. Canadian Journal of Zoology, 74, 606–620. doi:10.1139/z96-070.

    CAS  Google Scholar 

  • Rollo, C. D., Foss, J., Lachmansingh, E. I., & Singh, R. (1997a). Behavioural rhythmicity in transgenic growth hormone mice: Tradeoffs, energetics, and sleep-wake cycles. Canadian Journal of Zoology, 75, 20–34.

    Google Scholar 

  • Rollo, C. D., Kajiura, L., Wylie, B., & D’Souza, S. (1999a). The growth hormone axis, feeding, and central allocative regulation: Lessons from giant transgenic growth hormone mice. Canadian Journal of Zoology, 77, 1861–1873. doi:10.1139/cjz-77-12-1861.

    CAS  Google Scholar 

  • Rollo, C. D., Ko, C. V., Tyerman, J. G. A., & Kajiura, L. J. (1999b). The growth hormone axis and cognition: Empirical results and integrated theory derived from giant transgenic mice. Canadian Journal of Zoology, 77, 1874–1890. doi:10.1139/cjz-77-12-1874.

    CAS  Google Scholar 

  • Rollo, C. D., Lai, M., Whitehead, K., Perreault, M. L., Lemon, J., & Chaudhry, A. M. (2004). Thermoregulation of transgenic growth hormone mice. Canadian Journal of Zoology, 82, 934–949. doi:10.1139/z04-052.

    CAS  Google Scholar 

  • Rollo, C. D., Rintoul, J., & Kajiura, L. J. (1997b). Lifetime reproduction of giant transgenic mice: The energy stress paradigm. Canadian Journal of Zoology, 75, 1336–1345. doi:10.1139/z97-758.

    Google Scholar 

  • Sakic, B., Szechtman, H., Talangbayan, H., Denburg, S. D., Carbotte, R. M., & Denburg, J. A. (1994). Disturbed emotionality in autoimmune MRL-lpr mice. Physiology & Behavior, 56, 609–617. doi:10.1016/0031-9384(94)90309-3.

    CAS  Google Scholar 

  • Schieke, S. M., Phillips, D., McCoy, J. P., Jr, Aponte, A. M., Shen, R. F., Balaban, R. S., et al. (2006). The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. The Journal of Biological Chemistry, 281, 27643–27652. doi:10.1074/jbc.M603536200.

    PubMed  CAS  Google Scholar 

  • Schirmer, M., Nobrega, J. N., Harrison, S. J., & Loscher, W. (2007). Alterations in dopamine D3 receptors in the circling (ci3) rat mutant. Neuroscience, 144, 1462–1469. doi:10.1016/j.neuroscience.2006.11.022.

    PubMed  CAS  Google Scholar 

  • Schmaulhausen, I. I. (1949). Factors of evolution: The theory of stabilizing selection. Philadelphia: The Blakiston Co.

    Google Scholar 

  • Schulz, J. B., Lindenau, J., Seyfried, J., & Dichgans, J. (2000). Glutathione, oxidative stress and neurodegeneration. European Journal of Biochemistry, 267, 4904–4911. doi:10.1046/j.1432-1327.2000.01595.x.

    PubMed  CAS  Google Scholar 

  • Schwarting, R. K. W., & Huston, J. P. (1996). The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Progress in Neurobiology, 50, 275–331. doi:10.1016/S0301-0082(96)00040-8.

    PubMed  CAS  Google Scholar 

  • Schweitzer, P., Madamba, S. G., & Siggins, G. R. (1998). Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons. Journal of Neurophysiology, 79, 1230–1238.

    PubMed  CAS  Google Scholar 

  • Serrano, F., Kolluri, N. S., Wientjes, F. B., Card, J. P., & Klann, E. (2003). NADPH oxidase immunoreactivity in the mouse brain. Brain Research, 988, 193–198. doi:10.1016/S0006-8993(03)03364-X.

    PubMed  CAS  Google Scholar 

  • Smiragalia, D. J., Wu, C., Ellsworth, M. K., Ratty, A. K., Chapman, V. N., & Gross, K. W. (1997). Genetic characterization of the chromosomal rearrangements that accompany the transgene insertion in the Chakragati mouse mutant. Genomics, 45, 572–579. doi:10.1006/geno.1997.4976.

    Google Scholar 

  • Soderpalm, B., Ericson, M., Bohlooly, M., Engel, J. A., & Tornell, J. (1999). Bovine growth hormone transgenic mice display alterations in locomotor activity and brain monoamine neurochemistry. Endocrinology, 140, 5619–5625. doi:10.1210/en.140.12.5619.

    PubMed  CAS  Google Scholar 

  • Soghomonian, J. J., & Chesselet, M. F. (1991). Lesions of the dopaminergic nigrostriatal pathway alter preprosomatostatin messenger RNA levels in the striatum, the entopeduncular nucleus and the lateral hypothalamus of the rat. Neuroscience, 42, 49–59. doi:10.1016/0306-4522(91)90149-I.

    PubMed  CAS  Google Scholar 

  • Sonntag, W. E., Bennett, C., Ingram, R., Donahue, A., Ingraham, J., Chen, H., et al. (2006). Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP levels in a model of adult-onset growth hormone deficiency. American Journal of Physiology. Endocrinology and Metabolism, 291, 604–610. doi:10.1152/ajpendo.00012.2006.

    Google Scholar 

  • Spielewoy, C., Roubert, C., Hamon, M., Nosten-Bertrand, M., Betancur, C., & Giros, B. (2000). Behavioural disturbances associated with hyperdopaminergia in dopamine-transporter knockout mice. Behavioural Pharmacology, 11, 279–290.

    PubMed  CAS  Google Scholar 

  • Stackman, R. W., Hammond, R. S., Linardatos, E., Gerlach, A., Maylie, J., & Adelman, J. P. (2002). Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding. The Journal of Neuroscience, 22, 10163–10171.

    PubMed  CAS  Google Scholar 

  • Stearns, S. C. (2000). Life history evolution: Successes, limitations, and prospects. Naturwissenschaften, 87, 476–486. doi:10.1007/s001140050763.

    PubMed  CAS  Google Scholar 

  • Steger, R. W., Bartke, A., & Cecim, M. (1993). Premature ageing in transgenic mice expressing different growth hormone genes. Journal of Reproduction and Fertility. Supplement, 46, 61–75.

    PubMed  CAS  Google Scholar 

  • Steger, R. W., Bartke, A., Parkening, T. A., Collins, T., Buonomos, F. C., Tang, K., et al. (1991). Effects of heterologous growth hormones on hypothalamic and pituitary function in transgenic mice. Neuroendocrinology, 53, 365–372. doi:10.1159/000125743.

    PubMed  CAS  Google Scholar 

  • Strittmatter, M., Isenberg, E., Grauer, M. T., Hamann, G., & Schimrigk, K. (1996). CSF substance P, somatostatin and monoaminergic transmitter metabolites in patients with narcolepsy. Neuroscience Report, 218, 99–102.

    CAS  Google Scholar 

  • Sutcliffe, J. D., & de Lecea, L. (2002). The hypocretins: Setting the arousal threshold. Nature Reviews. Neuroscience, 3, 339–349. doi:10.1038/nrn808.

    PubMed  CAS  Google Scholar 

  • Svensson, J., Soderpalm, B., Sjogren, K., Engel, J., & Ohlsson, C. (2005). Liver-derived IGF-1 regulates exploratory activity in old mice. American Journal of Physiology. Endocrinology and Metabolism, 289, E455–E473. doi:10.1152/ajpendo.00425.2004.

    Google Scholar 

  • Szczypka, M. S., Zhou, Q. Y., & Palmiter, R. D. (1998). Dopamine-stimulated sexual behavior is testosterone dependent in mice. Behavioral Neuroscience, 112, 1229–1235. doi:10.1037/0735-7044.112.5.1229.

    PubMed  CAS  Google Scholar 

  • Szechtman, H. (1988). Effect of dopamine receptor agonist apomorphine on sensory input. Naunyn-Schmiedeberg’s Archives of Pharmacology, 338, 489–496. doi:10.1007/BF00179319.

    PubMed  CAS  Google Scholar 

  • Sziraki, I., Mohanakumar, K. P., Rauhala, P., Kim, H. G., Yeh, K. J., & Chiueh, C. C. (1998). Manganese: A transition metal protects nigrostriatal neurons from oxidative stress in the iron-induced animal model of Parkinsonism. Neuroscience, 85, 1101–1111. doi:10.1016/S0306-4522(97)00660-X.

    PubMed  CAS  Google Scholar 

  • Tang, Y. P., Shimizu, E., Dube, G. R., Rampon, C., Kerchner, G. A., Zhuo, M., et al. (1999). Genetic enhancement of learning and memory in mice. Nature, 401, 63–69. doi:10.1038/43432.

    PubMed  CAS  Google Scholar 

  • Taylor, B. A. (1976). Epistatic circling gene of C57L/J. Mouse News Letter, 55, 17.

    Google Scholar 

  • Tejada-Simon, M. V., Serrano, F., Villasana, L. E., Kanterewicz, B. I., Wu, G. Y., Quinn, M. T., et al. (2005). Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. Molecular and Cellular Neurosciences, 29, 97–106. doi:10.1016/j.mcn.2005.01.007.

    PubMed  CAS  Google Scholar 

  • Torres, G., Hallas, B. H., Vernace, V. A., Jones, C., Gross, K. W., & Horowitz, J. M. (2004). A neurobehavioral screening of the ckr mouse mutant: Implications for an animal model of schizophrenia. Brain Research Bulletin, 62, 315–326. doi:10.1016/j.brainresbull.2003.09.020.

    PubMed  CAS  Google Scholar 

  • Truett, G. E., Brock, J. W., Lidl, G. M., & Kloster, C. A. (1994). Stargazer (stg), new deafness mutant in the Zucker rat. Laboratory Animal Science, 44, 595–599.

    PubMed  CAS  Google Scholar 

  • Vezzani, A., & Hoyer, D. (1999). Brain somatostatin: A candidate inhibitory role in seizures and epileptogenesis. The European Journal of Neuroscience, 11, 3767–3776.

    PubMed  CAS  Google Scholar 

  • Vyazovskiy, V. V., Deboer, T., Rudy, B., Lau, D., Borbely, A. A., & Tobler, I. (2002). Sleep EEG in mice that are deficient in the potassium channel subunit K.v.3.2. Brain Research, 947, 204–211. doi:10.1016/S0006-8993(02)02925-6.

    PubMed  CAS  Google Scholar 

  • Waddington, C. H. (1957). The strategy of the genes. London: George Allen and Unwin.

    Google Scholar 

  • Wagner, E. F., Covarrubias, L., Stewart, T. A., & Mintz, B. (1983). Prenatal lethalities in mice homozygous for human growth hormone gene sequences integrated in the germ line. Cell, 35, 647–655. doi:10.1016/0092-8674(83)90097-1.

    PubMed  CAS  Google Scholar 

  • Weaver, I. C. G., Champagne, F. A., Brown, S. E., Dymov, S., Sharma, S., Meaney, M. J., et al. (2005). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: Altering epigenetic marking later in life. Neuroscience, 25, 11045–11054. doi:10.1523/JNEUROSCI.3652-05.2005.

    PubMed  CAS  Google Scholar 

  • Weimar, W. R., Lane, P. W., & Sidman, R. L. (1982). Vibrator (vb): A spinocerebellar system degeneration with autosomal recessive inheritance in mice. Brain Research, 251, 357–364. doi:10.1016/0006-8993(82)90754-5.

    PubMed  CAS  Google Scholar 

  • Weltman, A. S., Sackler, A. M., Lewis, A. S., & Johnson, L. (1970). Metabolism rate biochemical and endocrine alterations in male whirler mice. Physiology & Behavior, 5, 17–22. doi:10.1016/0031-9384(70)90006-5.

    CAS  Google Scholar 

  • Wenthold, R. J., & Gulley, R. L. (1978). Glutamic acid and aspartic acid in the cochlear nucleus of the waltzing Guinea pig. Brain Research, 158, 295–302. doi:10.1016/0006-8993(78)90676-5.

    PubMed  CAS  Google Scholar 

  • West-Eberhard, M. J. (2003). Developmental plasticity and evolution. New York: Oxford University Press.

    Google Scholar 

  • Wilson, M. C. (2000). Coloboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder. Neuroscience and Biobehavioral Reviews, 24, 51–57. doi:10.1016/S0149-7634(99)00064-0.

    PubMed  CAS  Google Scholar 

  • Wonderlin, W. F., & Strobl, J. S. (1996). Potassium channels, proliferation and G1 progression. The Journal of Membrane Biology, 154, 91–107. doi:10.1007/s002329900135.

    PubMed  CAS  Google Scholar 

  • Xu, R., Roh, S. G., Loneragan, K., Pullar, M., & Chen, C. (1999). Human GHRH reduces voltage-gated K+ currents via a non-cAMP-dependent but PKC-mediated pathway in human GH adenoma cells. The Journal of Physiology, 520, 697–707. doi:10.1111/j.1469-7793.1999.00697.x.

    PubMed  CAS  Google Scholar 

  • Yamanaka, A., Beuckmann, C. T., Willie, J. T., Hara, J., Tsujino, N., Mieda, M., et al. (2003). Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron, 38, 701–713. doi:10.1016/S0896-6273(03)00331-3.

    PubMed  CAS  Google Scholar 

  • Young, K. A., Berry, M. L., Mahaffey, C. L., Saionz, J. R., Hawes, N. L., Chang, B., et al. (2002). Fierce: A new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background dependent. Behavioural Brain Research, 132, 145–158. doi:10.1016/S0166-4328(01)00413-2.

    PubMed  CAS  Google Scholar 

  • Zavitsanou, K., Triarhou, L. C., Kouvelas, E. D., Mitsacos, A., Palacios, J. M., & Mengod, G. (2002). Somatostatin, cholecystokinin and neuropeptide Y mRNAs in normal and weaver mouse brain. Journal of Neural Transmission, 109, 1337–1351. doi:10.1007/s00702-002-0759-7.

    PubMed  CAS  Google Scholar 

  • Zhang, Y., Vilaythong, A. P., Yoshor, D., & Noebels, J. L. (2004). Elevated thalamic low-voltage-activated currents precede the onset of absence epilepsy in the SNAP25-deficient mouse mutant Coloboma. The Journal of Neuroscience, 24, 5239–5248. doi:10.1523/JNEUROSCI.0992-04.2004.

    PubMed  CAS  Google Scholar 

  • Ziegler, M., & Szechtman, H. (1988). Differences in the behavioral profile of circling under amphetamine and apomorphine in rats with unilateral lesions of the substantia nigra. Behavioral Neuroscience, 102, 276–288. doi:10.1037/0735-7044.102.2.276.

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge that they have no conflicts of interest. The Natural Sciences and Engineering Research Council of Canada (RGPIN A0544) and Canadian Institutes for Health Research (MOP-64424) provided funding. Dr. Jack Rosenfeld provided assistance and training for the HPLC. We thank our editor (Dr. B. Hallgrimsson) and two anonymous reviewers who emphasised the value of demonstrating that selection had occurred in the transgenic growth hormone mice and for other critical comments that greatly improved this manuscript.

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  1. Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8S 4K1

    A. M. Chaudhry, S. E. Marsh-Rollo, V. Aksenov & C. D. Rollo

  2. Department of Psychiatry & Behavioural Neurosciences, McMaster University, 1200 Main St. W., Hamilton, ON, Canada, L8N 3Z5

    A. M. Chaudhry & H. Szechtman

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  1. A. M. Chaudhry
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Correspondence to C. D. Rollo.

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Chaudhry, A.M., Marsh-Rollo, S.E., Aksenov, V. et al. Modifier Selection by Transgenes: The Case of Growth Hormone Transgenesis and Hyperactive Circling Mice. Evol Biol 35, 267–286 (2008). https://doi.org/10.1007/s11692-008-9036-5

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