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Mammalian Genome

, Volume 16, Issue 7, pp 505–515 | Cite as

QTL mapping for traits associated with stress neuroendocrine reactivity in rats

  • Bastien Llamas
  • Vincent Contesse
  • Véronique Guyonnet–Duperat
  • Hubert Vaudry
  • Pierre Mormède
  • Marie-Pierre MoisanEmail author
Article

Abstract

In the present study we searched for quantitative trait loci (QTLs) that affect neuroendocrine stress responses in a 20-min restraint stress paradigm using Brown–Norway (BN) and Wistar–Kyoto–Hyperactive (WKHA) rats. These strains differed in their hypothalamic–pituitary–adrenal axis (plasma ACTH and corticosterone levels, thymus, and adrenal weights) and in their renin–angiotensin–aldosterone system reactivity (plasma renin activity, aldosterone concentration). We performed a whole-genome scan on a F2 progeny derived from a WKHA × BN intercross, which led to the identification of several QTLs linked to plasma renin activity (Sr6, Sr8, Sr11, and Sr12 on chromosomes RNO2, 3, 19, and 8, respectively), plasma aldosterone concentration (Sr7 and Sr9 on RNO2 and 5, respectively), and thymus weight (Sr10, Sr13, and Srl4 on RNO5, 10, and 16, respectively). The type 1b angiotensin II receptor gene (Agtrlb) maps within the confidence intervals of QTLs on RNO2 linked to plasma renin activity (Sr6, highly significant; LOD = 5.0) and to plasma aldosterone level (Sr7, suggestive; LOD = 2.0). In vitro studies of angiotensin II–induced release of aldosterone by adrenal glomerulosa cells revealed a lower receptor potency (log EC50 = −8.16 ± 0.11 M) and efficiency (Emax = 453.3 ± 25.9 pg/3 × 104 cells/24 h) in BN than in WKHA (log EC50 = −10.66 ± 0.18 M; Emax = 573.1 ± 15.3 pg/3 × 104 cells/24 h). Moreover, differences in Agtr1b mRNA abundance and sequence reinforce the putative role of the Agtr1b gene in the differential plasma renin stress reactivity between the two rat strains.

Keywords

Quantitative Trait Locus Aldosterone Plasma Renin Activity Mineralocorticoid Receptor Suggestive Quantitative Trait Locus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Ahmadiyeh N, Churchill GA, Shimomura K, Solberg LC, Takahashi JS, et al. (2003) X-linked and lineage-dependent inheritance of coping responses to stress Mamm Genome 14: 748–757CrossRefPubMedGoogle Scholar
  2. Altmuller J, Palmer LJ, Fischer G, Scherb H, Wjst M (2001) Genomewide scans of complex human diseases: true linkage is hard to find Am J Hum Genet 69: 936–950CrossRefPubMedGoogle Scholar
  3. Armando I, Carranza A, Nishimura Y, Hoe KL, Barontini M, et al. (2001) Peripheral administration of an angiotensin II AT(1) receptor antagonist decreases the hypothalamic–pituitary–adrenal response to isolation stress endocrinology 142: 3880–3889CrossRefPubMedGoogle Scholar
  4. Armario A, Gavalda A, Marti J (1995) Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats Psychoneuroendocrinology 20: 879–890CrossRefPubMedGoogle Scholar
  5. Balla T, Baukal AJ, Eng S, Catt KJ (1991) Angiotensin II receptor subtypes and biological responses in the adrenal cortex and medulla Mol Pharmacol 40: 401–406PubMedGoogle Scholar
  6. Cannon WB (1935) Stresses and strains of homeostasis Am J Med Sci 189: 1–14Google Scholar
  7. Castanon N, Hendley ED, Fan XM, Mormede P (1993) Psychoneuroendocrine profile associated with hypertension or hyperactivity in spontaneously hypertensive rats Am J Physiol 265: R1304–R1310PubMedGoogle Scholar
  8. Challah M, Villard E, Philippe M, Ribadeau–Dumas A, Giraudeau B, et al. (1998) Angiotensin I–converting enzyme genotype influences arterial response to injury in normotensive rats Arterioscler Thromb Vase Biol 18: 235–243Google Scholar
  9. Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping Genetics 138: 963–971PubMedGoogle Scholar
  10. Courvoisier H, Moisan MP, Sarrieau A, Hendley ED, Mormède P (1996) Behavioral and neuroendocrine reactivity to stress in the WKHA/WKY inbred rat strains: a multifactorial and genetic analysis Brain Res 743: 77–85CrossRefPubMedGoogle Scholar
  11. Cui ZH, Ikeda K, Kawakami K, Gonda T, Nabika T, et al. (2003) Exaggerated response to restraint stress in rats congenic for the chromosome 1 blood pressure quantitative trait locus Clin Exp Pharmacol Physiol 30: 464–469CrossRefPubMedGoogle Scholar
  12. Darvasi A, Soller M (1997) A simple method to calculate resolving power and confidence interval of QTL map location Behav Genet 27: 125–132CrossRefPubMedGoogle Scholar
  13. de Baey A, Lanzavecchia A (2000) The role of aquaporins in dendritic cell macropinocytosis J Exp Med 191: 743–748CrossRefPubMedGoogle Scholar
  14. Di Nicolantonio R, Kotstka V, Chow MZ, Jansa P, Harrap SB (2003) The Lvm-1 locus controlling left ventricular size contains a variant of the angiotensin II type 1b receptor. Physiological Genomics & Rat Models. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory PressGoogle Scholar
  15. Dumas P, Pausova Z, Kren V, Krenova D, Pravenec M, et al. (2000) Contribution of autosomal loci and the Y chromosome to the stress response in rats Hypertension 35: 568–573PubMedGoogle Scholar
  16. Ehlert U, Gaab J, Heinrichs M (2001) Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis Biol Psychol 57: 141–152CrossRefPubMedGoogle Scholar
  17. Feraandez–Terael A, Escorihuela RM, Gray JA, Aguilar R, Gil L, et al. (2002) A quantitative trait locus influencing anxiety in the laboratory rat Genome Res 12: 618–626PubMedGoogle Scholar
  18. Gasc JM, Shanmugam S, Sibony M, Corvol P (1994) Tissue-specific expression of type 1 angiotensin n receptor subtypes. An in situ hybridization study Hypertension 24: 531–537PubMedGoogle Scholar
  19. Gigante B, Rubattu S, Russo R, Porcellini A, Enea I, et al. (1997) Opposite feedback control of renin and aldosterone biosynthesis in the adrenal cortex by angiotensin II AT1-subtype receptors Hypertension 30: 563–568PubMedGoogle Scholar
  20. Glazier AM, Nadeau JH, Aitman TJ (2002) Finding genes that underlie complex traits Science 298: 2345–2349PubMedGoogle Scholar
  21. Golin RM, Gotoh E, Said SI, Ganong WF (1988) Pharmacological evidence that the sympathetic nervous system mediates the increase in renin secretion produced by immobilization and head-up tilt in rats Neuropharmacology 27: 1209–1213CrossRefPubMedGoogle Scholar
  22. Gomez F, Lahmame A, De Kloet ER, Armario A (1996) Hypothalamic–pituitary–adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level Neuroendocrinology 63: 327–337PubMedGoogle Scholar
  23. Haley CS, Knott SA (1992) A simple Regression method for mapping quantitative trait loci in line Crosses using flanking markers Heredity 69: 315–324Google Scholar
  24. Hendley ED, Ohlsson WG (1991) Two new inbred rat strains derived from SHR: WKHA, hyperactive, and WKHT, hypertensive, rats Am J Physiol 261: H583–H589PubMedGoogle Scholar
  25. Inglis GC, Ingram MC, Holloway CD, Swan L, Birnie D, et al. (1999) Familial pattern of corticosteroids and their metabolism in adult human subjects—the Scottish Adult Twin Study J Clin Endocrinol Metab 84: 4132–4137CrossRefPubMedGoogle Scholar
  26. Innes BA, McLaughlin MG, Kapuscinski MK, Jacob HJ, Harrap SB (1998) Independent genetic susceptibility to cardiac hypertrophy in inherited hypertension Hypertension 31: 741–746PubMedGoogle Scholar
  27. Jablonski EM, Webb AN, McConnell NA, Riley MC, Hughes FM, Jr (2004) Plasma membrane aquaporin activity can affect the rate of apoptosis but is inhibited after apoptotic volume decrease Am J Physiol Cell Physiol 286: C975–C985CrossRefPubMedGoogle Scholar
  28. Johren O, Golsch C, Dendorfer A, Qadri F, Hauser W, et al. (2003) Differential expression of AT1 receptors in the pituitary and adrenal gland of SHR and WKY Hypertension 41: 984–990CrossRefPubMedGoogle Scholar
  29. Kakar SS, Sellers JC, Devor DC, Musgrove LC, Neill JD (1992) Angiotensin II type-1 receptor subtype cDNAs: differential tissue expression and hormonal regulation Biochem Biophys Res Commun 183: 1090–1096CrossRefPubMedGoogle Scholar
  30. Klar J, Vitzthum H, Kurtz A (2004) Aldosterone enhances renin gene expression in juxtaglomerular cells Am J Physiol Renal Physiol 286: F349–F355CrossRefPubMedGoogle Scholar
  31. Korstanje R, Paigen B (2002) From QTL to gene: the harvest begins Nat Genet 31:235–236CrossRefPubMedGoogle Scholar
  32. Lander ES, Botstein D (1989) Mapping mendelian factors underlying quantitative traits using RFLP linkage maps Genetics 121: 185–199PubMedGoogle Scholar
  33. Lander E, Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results Nat Genet 11: 241–247CrossRefPubMedGoogle Scholar
  34. Lander ES, Schork NJ (1994) Genetic dissection of complex traits Science 265: 2037–2048PubMedGoogle Scholar
  35. Leboulenger F, Delarue C, Belanger A, Perroteau I, Netchitailo P, et al. (1982) Direct radioimmunoassay for plasma corticosterone and aldosterone in frog. I. Validation of the methods and evidence for daily rhythms in a natural environment Gen Comp Endocrinol 46: 521–532CrossRefPubMedGoogle Scholar
  36. Lenglet S, Louiset E, Delarue C, Vaudry H, Contesse V (2002) Activation of 5-HT(7) receptor in rat glomerulosa cells is associated with an increase in adenylyl cyclase activity and calcium influx through T-type calcium channels Endocrinology 143: 1748–1760CrossRefPubMedGoogle Scholar
  37. Lenkei Z, Palkovits M, Corvol P, Llorens–Cortes C (1998) Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain Neuroscience 82: 827–841CrossRefPubMedGoogle Scholar
  38. Leong DS, Terron JA, Falcon–Neri A, Armando I, Ito T, et al. (2002) Restraint stress modulates brain, pituitary and adrenal expression of angiotensin II AT(1A), AT(1B) and AT(2) receptors Neuroendocrinology 75: 227–240CrossRefPubMedGoogle Scholar
  39. Manly KF, Cudmore RH, Jr, Meer JM (2001) Map Manager QTX, cross-platform software for genetic mapping Mamm Genome 12: 930–932CrossRefPubMedGoogle Scholar
  40. Marissal–Arvy N, Mormède P, Sarrieau A (1999) Strain differences in corticosteroid receptor efficiencies and regulation hi Brown Norway and Fischer 344 rats J Neuroendocrinol 11: 267–273CrossRefPubMedGoogle Scholar
  41. Marissal-Arvy N, Ribot E, Sarrieau A, Mormede P (2000) Is the mineralocorticoid receptor in Brown Norway rats constitutively active? J Neuroendocrinol 12: 576–588CrossRefPubMedGoogle Scholar
  42. Marissal-Arvy N, Lombes M, Petterson J, Moisan MP, Mormède P (2004) Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat J Biol Chem 279: 39232–39239CrossRefPubMedGoogle Scholar
  43. Matsuzaki T, Tajika Y, Tserentsoodol N, Suzuki T, Aoki T, et al. (2002) Aquaporins: a water channel family Anat Sci Int 77: 85–93CrossRefPubMedGoogle Scholar
  44. McCarty R, Kirby RF, Garn PG (1984) Strain differences in sympathetic-adrenal medullary responsiveness and behavior Behav Neurol Biol 40: 98–113CrossRefGoogle Scholar
  45. Moisan MP, Courvoisier H, Bihoreau MT, Gauguier D, Hendley ED, et al. (1996) A major quantitative trait locus influences hyperactivity in the WKHA rat Nat Genet 14: 471–473CrossRefPubMedGoogle Scholar
  46. Moisan MP, Llamas B, Cook MN, Mormède P (2003) Further dissection of a genomic locus associated with behavioral activity in the Wistar–Kyoto hyperactive rat, an animal model of hyperkinesis Mol Psychiatry 8: 348–352CrossRefPubMedGoogle Scholar
  47. Mormède P, Courvoisier H, Ramos A, Marissal–Arvy N, Ousova O, et al. (2002) Molecular genetic approaches to investigate individual variations in behavioral and neuroendocrine stress responses Psychoneuroendocrinology 27: 563–583CrossRefPubMedGoogle Scholar
  48. Murillo-Carretero MI, Ilundain AA, Echevarria M (1999) Regulation of aquaporin mRNA expression in rat kidney by water intake J Am Soc Nephrol 10: 696–703PubMedGoogle Scholar
  49. Paris JM, Lorens SA, Van de Kar LD, Urban JH, Richardson–Morton KD, et al. (1987) A comparison of acute stress paradigms: hormonal responses and hypothalamic serotonin Physiol Behav 39: 33–43CrossRefPubMedGoogle Scholar
  50. Potenza MN, Brodkui ES, Joe B, Luo X, Remmers E, et al. (2004) Genomic regions controllhig corticosterone levels in rats Biol Psychiatry 55: 634–641CrossRefPubMedGoogle Scholar
  51. Ramos A, Moisan MP, Chaouloff F, Mormède C, Mormède P (1999) Identification of female-specific QTLs affecting an emotionality- related behavior hi rats Mol Psychiatry 4: 453–462CrossRefPubMedGoogle Scholar
  52. Sambrook J. Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory PressGoogle Scholar
  53. Sarrieau A, Mormède P (1998) Hypothalamic–pituitary–adrenal axis activity in the inbred Brown Norway and Fischer 344 rat strains Life Sci 62: 1417–1425CrossRefPubMedGoogle Scholar
  54. Sarrieau A, Chaouloff F, Lemaire V, Mormède P (1998) Comparison of the neuroendocrine responses to stress in outbred, inbred and F1 hybrid rats Life Sci 63: 87–96CrossRefPubMedGoogle Scholar
  55. Selye H (1973) The evolution of the concept of stress Am Sci 61: 692–699PubMedGoogle Scholar
  56. Sigg EB, Keim KL, Sigg TD (1978) On the mechanism of renin release by restraint stress hi rats Pharmacol Biochem Behav 8: 47–50CrossRefPubMedGoogle Scholar
  57. Sowers J, Tuck M, Asp ND, Sollars E (1981) Plasma aldosterone and corticosterone responses to adrenocorticotropin, angiotensin, potassium, and stress in spontaneously hypertensive rats endocrinology 108: 1216–1221PubMedGoogle Scholar
  58. Steckler T (2001) The molecular neurobiology of stress—evidence from genetic and epigenetic models Behav Pharmacol 12: 381–427PubMedGoogle Scholar
  59. Visscher PM, Thompson R, Haley CS (1996) Confidence intervals in QTL mapping by bootstrapping Genetics 143: 1013–1020PubMedGoogle Scholar
  60. Walling GA, Visscher PM, Haley CS (1998) A comparison of bootstrap methods to construct confidence intervals in QTL mapping Genet Res 71: 171–180CrossRefGoogle Scholar
  61. Williams PD, Puddey IB, Beilin LJ, Vandongen R (1993) Genetic influences on plasma catecholamines in human twins J Clin Endocrinol Metab 77: 794–799CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Bastien Llamas
    • 1
  • Vincent Contesse
    • 2
  • Véronique Guyonnet–Duperat
    • 1
  • Hubert Vaudry
    • 2
  • Pierre Mormède
    • 1
  • Marie-Pierre Moisan
    • 1
    Email author
  1. 1.Laboratoire Neurogénétique et StressINSERM U471/INRA UMR1243, Université Victor Segalen Bordeaux 2, Institut François MagendiecedexFrance
  2. 2.Laboratory of Cellular and Molecular NeuroendocrinologyEuropean Institute for Peptide Research, IFRMP 23, INSERM U413,UA CNRS, University of RouencedexFrance

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