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Systemic First-Line Phenotyping

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Abstract

 With the completion of the mouse genome sequence an essential task for biomedical sciences in the twenty-first century will be the generation and functional analysis of mouse models for every gene in the mammalian genome. More than 30,000 mutations in ES cells will be engineered and thousands of mouse disease models will become available over the coming years by the collaborative effort of the International Mouse Knockout Consortium. In order to realize the full value of the mouse models proper characterization, archiving and dissemination of mouse disease models to the research community have to be performed. Phenotyping centers (mouse clinics) provide the necessary capacity, broad expertise, equipment, and infrastructure to carry out large-scale systemic first-line phenotyping. Using the example of the German Mouse Clinic (GMC) we will introduce the reader to the different aspects of the organization of a mouse clinic and present selected methods used in first-line phenotyping.

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    *Equal contribution

References

  1. Collins FS, Rossant J, Wurst W. A mouse for all reasons. Cell 2007; 128:9–13.

    Article  PubMed  CAS  Google Scholar 

  2. Rosenthal N, Brown S. The mouse ascending: perspectives for human-disease models. Nat Cell Biol 2007; 9:993–9.

    Article  PubMed  CAS  Google Scholar 

  3. Brown SD, Hancock JM, Gates H. Understanding mammalian genetic systems: the challenge of phenotyping in the mouse. PLoS Genet 2006; 2:e118

    Article  PubMed  CAS  Google Scholar 

  4. Gailus-Durner V, Fuchs H, Becker L, Bolle I, et al. Introducing the German Mouse Clinic: open access platform for standardized phenotyping. Nat Meth 2005; 2:403–4.

    Article  CAS  Google Scholar 

  5. Brown SD, Chambon P, Hrabé de Angelis M, Eumorphia Consortium. EMPReSS: standardized phenotype screens for functional annotation of the mouse genome. Nat Genet 2005; 37:1155.

    Article  PubMed  CAS  Google Scholar 

  6. Brielmeier M, Mahabir E, Needham JR, Lengger C, Wilhelm P, Schmidt J. Microbiological monitoring of laboratory mice and biocontainment in individually ventilated cages: a field study. Lab Anim 2006; 40:247–60.

    Article  PubMed  CAS  Google Scholar 

  7. Maier H, Lengger Ch, Simic B, Fuchs H, Gailus-Durner V, Hrabé de Angelis M. MausDB: an open source application for phenotype data and mouse colony management in large-scale mouse phenotyping projects. BMC Bioinformatics 2008; 9:169 (epub 26 March 2008)

    Article  PubMed  CAS  Google Scholar 

  8. The Mouse Phenotype Database Integration Consortium. Integration of mouse phenome data resources. The Mouse Phenotype Database Integration Consortium. Mamm Genome 2007; 18:157–63.

    Google Scholar 

  9. WHO. The World Health Report 2001 – Mental Health: New Understanding, New Hope; http://www.who.int/whr/2001/en/index.html.

  10. Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2002; 2:389–406.

    Article  PubMed  CAS  Google Scholar 

  11. Ralston SH, de Crombrugghe B. Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 2006; 20:2492–506.

    Article  PubMed  CAS  Google Scholar 

  12. Abe K., Fuchs H., Lisse T., Hans W. and Hrabé de Angelis M. New ENU induced semidominant mutation, Ali18, causes inflammatory arthritis, dermatitis, and osteoporosis in the mouse. Mamm Genome 2006; 17:915–26.

    Article  PubMed  CAS  Google Scholar 

  13. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004; 363:1377–85.

    Article  PubMed  CAS  Google Scholar 

  14. Giampietro PF, Blank RD, Raggio CL, et al. Congenital and idiopathic scoliosis: clinical and genetic aspects. Clin Med Res 2003; 1:125–36.

    Article  PubMed  Google Scholar 

  15. Mariani FV, Martin GR. Deciphering skeletal patterning: clues from the limb. Nature 2003; 423: 19–25.

    Article  CAS  Google Scholar 

  16. Fuchs H, Schughart K, Wolf E, Balling R, Hrabé de Angelis M. Screening for dysmorphological abnormalities – a powerful tool to isolate new mouse mutants. Mamm Genome 2000; 11:528–30.

    Article  PubMed  CAS  Google Scholar 

  17. Sorenson JA, Duke PR, Smith SW. Simulation studies of dual-energy X-ray absorptiometry. Med Phys 1989; 16:75–80

    Article  PubMed  CAS  Google Scholar 

  18. Gasser JA. Bone measurements by peripheral quantitative computed tomography in rodents. Methods Mol Med 2003; 80:323–41.

    PubMed  Google Scholar 

  19. Turner CH, Hsieh YF, Muller R et al. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res 2000; 15:1126–31

    Article  PubMed  CAS  Google Scholar 

  20. Allen MJ. Biochemical markers of bone metabolism in animals: uses and limitations. Vet. Clinical Path 2003; 32:101–113

    Article  CAS  Google Scholar 

  21. Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone 1993; 14:595–608.

    Article  PubMed  CAS  Google Scholar 

  22. Akhter MP, Iwaniec UT, Covey MA, Cullen DM, Kimmel DB, Recker RR. Genetic variations in bone density, histomorphometry, and strength in mice. Calcif Tissue Int 2000; 67:337–44.

    Article  PubMed  CAS  Google Scholar 

  23. Roman-Roman S, Garcia T., Jackson A, et al. Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro. Bone 2003; 32:474–82.

    Article  PubMed  CAS  Google Scholar 

  24. Umemura Y, Baylink DJ, Wergedal JE, Mohan S, Srivastava AK. A time course of bone response to jump exercise in C57BL/6 J mice. J Bone Miner Metab 2002; 20:209–15.

    Article  PubMed  Google Scholar 

  25. Robling AG, Turner CH. Mechanotransduction in bone: genetic effects on mechanosensitivity in mice. Bone 2002; 31:562–9.

    Article  PubMed  CAS  Google Scholar 

  26. Rubin C, Turner AS, Bain S, Mallinckrodt C, McLeod K. Low mechanical signals strengthen long bones. Nature 2001; 412:603–4.

    Article  PubMed  CAS  Google Scholar 

  27. Hoshi A, Watanabe H, Chiba M, Inaba Y. Effects of exercise at different ages on bone density and mechanical properties of femoral bone of aged mice. Tohoku J Exp Med 1998; 185:15–24.

    Article  PubMed  CAS  Google Scholar 

  28. Judex S, Donahue LR, Rubin C. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J 2002; 16:1280–2.

    PubMed  CAS  Google Scholar 

  29. Krege JH, Hodgin JB, Hagaman JR, Smithies O. A noninvasive computerized tail-cuff system for measuring blood pressure in mice. Hypertension 1995; 25:1111–5.

    PubMed  CAS  Google Scholar 

  30. Lorenz JN. A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice. Am J Physiol Regul Integr Comp Physiol 2002; 282:R1565–82.

    PubMed  CAS  Google Scholar 

  31. Deschepper CF, Olson JL, Otis M, Gallo-Payet N. Characterization of blood pressure and morphological traits in cardiovascular-related organs in 13 different inbred mouse strains. J Appl Physiol 2004; 97:369–76.

    Article  PubMed  Google Scholar 

  32. Lang RE, Unger T, Ganten D. Atrial natriuretic peptide: a new factor in blood pressure control. J Hypertens. 1987; 5:255–71.

    Article  PubMed  CAS  Google Scholar 

  33. Nishikimi T, Maeda N, Matsuoka H. The role of natriuretic peptides in cardioprotection. Cardiovasc Res 2006; 69:318–28.

    Article  PubMed  CAS  Google Scholar 

  34. Kilic A, Bubikat A, Gassner B, Baba HA, Kuhn M. Local actions of atrial natriuretic peptide counteract angiotensin II stimulated cardiac remodeling. Endocrinology 2007; 148:4162–9.

    Article  PubMed  CAS  Google Scholar 

  35. Yap LB, Mukerjee D, Timms PM, Ashrafian H, Coghlan JG. Natriuretic peptides, respiratory disease, and the right heart. Chest 2004; 126:1330–6.

    Article  PubMed  CAS  Google Scholar 

  36. Moro C, Berlan M. Cardiovascular and metabolic effects of natriuretic peptides. Fundam Clin Pharmacol 2006; 20:41–9.

    Article  PubMed  CAS  Google Scholar 

  37. Lerman A, Gibbons RJ, Rodeheffer RJ, et al. Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction. Lancet 1993; 341: 1105–9.

    Article  PubMed  CAS  Google Scholar 

  38. Kettunen RV, Leppaluoto J, Jounela A, Vuolteenaho O. Plasma N-terminal atrial natriuretic peptide in acute myocardial infarction. Am Heart J 1994; 127:1449–55.

    Article  PubMed  CAS  Google Scholar 

  39. Schoensiegel F, Bekeredjian R, Schrewe A, et al. Atrial natriuretic peptide (Nt-proANP) and osteopontin (Opn) are useful tools to screen for cardiac disorders in mice. Comp Med 2007; 57:546–53.

    PubMed  CAS  Google Scholar 

  40. Doevendans PA, Daemen MJ, de Muinck ED, Smits JF. Cardiovascular phenotyping in mice. Cardiovasc Res 1998; 39:34–49.

    Article  PubMed  CAS  Google Scholar 

  41. Ehmke H. Mouse gene targeting in cardiovascular physiology. Am J Physiol Regul Integr Comp Physiol 2003; 284:R28–30.

    PubMed  CAS  Google Scholar 

  42. Royer A, van Veen TA, Le Bouter S, et al. Mouse model of SCN5A-linked hereditary Lenegre’s disease: age-related conduction slowing and myocardial fibrosis. Circulation 2005; 111:1738–46.

    Article  PubMed  CAS  Google Scholar 

  43. Yang XP, Liu YH, Rhaleb NE, Kurihara N, Kim HE, Carretero OA. Echocardiographic assessment of cardiac function in conscious and anesthetized mice. Am J Physiol 1999; 277:H1967–74.

    PubMed  CAS  Google Scholar 

  44. Collins KA, Korcarz CE, Lang RM. Use of echocardiography for the phenotypic assessment of genetically altered mice. Physiol Genomics 2003; 13:227–39.

    PubMed  Google Scholar 

  45. Syed F, Diwan A, Hahn HS. Murine echocardiography: a practical approach for phenotyping genetically manipulated and surgically modeled mice. J Am Soc Echocardiogr 2005; 18:982–90.

    Article  PubMed  Google Scholar 

  46. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109:433–8

    Article  PubMed  Google Scholar 

  47. WHO. The World Health Report 2002 – Reducing Risks, Promoting Healthy Life. http://www.who.int/whr/2002/en/index.html.

  48. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer 2002; 2:862–71.

    Article  PubMed  CAS  Google Scholar 

  49. Meyer CW, Neubronner J, Rozman J. et al. Expanding the body mass range: associations between BMR and tissue morphology in wild type and mutant dwarf mice (David mice). J Comp Physiol [B] 2007; 177:183–92.

    Article  Google Scholar 

  50. Meyer CW, Elvert R, Scherag A, et al. Power matters in closing the phenotyping gap. Naturwissenschaften 2007; 94:401–6.

    Article  PubMed  CAS  Google Scholar 

  51. Kallnik M, Elvert R, Ehrhardt N, et al. Impact of IVC housing on emotionality and fear learning in male C3HeB/FeJ and C57BL/6 J mice. Mamm. Genome 2007; 18:173–86.

    Article  PubMed  Google Scholar 

  52. Haemmerle G, Lass A, Zimmermann R, et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006; 312:734–7.

    Article  PubMed  CAS  Google Scholar 

  53. WHO 2006, Mortality Data, http://www.who.int/whosis/mort/en/

  54. WHO 2005, Particulate matter and air pollution: how it harms health, http://www.euro.who.int/document/mediacentre/fs0405e.pdf

  55. European Respiratory Society & European Lung Foundation. The European lung white book. 2003 ERSJ Ltd, UK.

    Google Scholar 

  56. Reinhard C, Eder G, Fuchs H, Ziesenis A, Heyder J, Schulz H. Inbred strain variation in lung function. Mamm Genome 2002; 13:429–37.

    Article  PubMed  Google Scholar 

  57. Reinhard C, Meyer B, Fuchs H, et al. Genomewide linkage analysis identifies novel genetic loci for lung function in mice. Am J Respir Crit Care Med. 2005; 171:880–8.

    Article  PubMed  Google Scholar 

  58. Ganguly K, Stoeger T, Wesselkamper SC, et al. Candidate genes controlling pulmonary function in mice: transcript profiling and predicted protein structure. Physiol Genomics 2007; 31:410–21.

    Article  PubMed  CAS  Google Scholar 

  59. Tankersley CG. Genetic control of ventilation: What are we learning from murine models? Curr Opinion Pul Med 1999; 5:344–8.

    Article  CAS  Google Scholar 

  60. Tankersley CG, Fitzgerald RS, Levitt RC, Mitzner WA, Ewart SL Kleeberger SR. Genetic control of differential baseline breathing pattern. J Appl Physiol 1997; 82:874–81.

    PubMed  CAS  Google Scholar 

  61. Schulz, H., Johner, C., Eder, et al. Respiratory mechanics in mice: strain and sex specific differences. Acta Physiol Scand 2002; 174:367–75.

    Article  PubMed  CAS  Google Scholar 

  62. Alessandrini F, Schulz H, Takenaka S, et al. Effects of ultrafine carbon particle inhalation on allergic inflammation of the lung. J Allergy Clin Immunol 2006; 117:824–30.

    Article  PubMed  CAS  Google Scholar 

  63. Ohl F, Holsboer F, Landgraf R. The modified hole board as a differential screen for behavior in rodents. Behav Res Meth Instr Comp 2001; 33:392–7.

    Article  CAS  Google Scholar 

  64. Geyer MA. Assessing prepulse inhibition of startle in wild type and knockout mice. Psychopharmacology 1999; 147:11–3.

    Article  PubMed  CAS  Google Scholar 

  65. Belzung C, Griebel G. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 2001; 125:141–9.

    Article  PubMed  CAS  Google Scholar 

  66. Cryan JF, Holmes A. The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 2005; 4:775–90.

    Article  PubMed  CAS  Google Scholar 

  67. Engelmann M, Wotjak CT, Landgraf R. Social discrimination procedure: An alternative method to investigate juvenile recognition abilities in rats. Physiol Behav 1995; 58:315–21.

    Article  PubMed  CAS  Google Scholar 

  68. Richter K, Wolf G, Engelmann M. Social recognition memory requires two stages of protein synthesis in mice. Learn Mem 2005; 12:407–13.

    Article  PubMed  Google Scholar 

  69. Falls, W. Fear-potentiated startle in mice. In Crawley, J. (ed), Current Protocols in Neuroscience 2002. Unit 8.11B.1–8.11B.16.

    Google Scholar 

  70. Genoux D, Haditsch U, Knobloch M, Michalon A, Storm D, Mansuy I. Protein phosphatase 1 is a molecular constraint on learning and memory. Nature 2002; 418:970–5.

    Article  PubMed  CAS  Google Scholar 

  71. Hölter SM, Kallnik M, Wurst W, Marsicano G, Lutz B, Wotjak CT. Cannabinoid CB1 receptor is dispensable for memory extinction in an appetitively-motivated learning task. Eur J Pharmacol 2005; 510:69–74.

    Article  PubMed  CAS  Google Scholar 

  72. Watase K, Zoghbi HY. Modelling brain diseases in mice: the challenges of design and analysis. Nat Rev Genet 2003; 4:296–307.

    Article  PubMed  CAS  Google Scholar 

  73. Oliver PL, Davies KE. Analysis of human neurological disorders using mutagenesis in the mouse. Clin Sci (Lond) 2005; 108:385–97.

    Article  CAS  Google Scholar 

  74. Schneider I, Tirsch WS, Faus-Kessler T, et al. Systematic, standardized and comprehensive neurological phenotyping of inbred mice strains in the German Mouse Clinic. J Neurosci Methods 2006; 157:82–90.

    Article  PubMed  Google Scholar 

  75. Rogers DC, Fisher EM, Brown SD, Peters J, Hunter AJ, Martin JE. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm Genome 1997; 8:711–3.

    Article  PubMed  CAS  Google Scholar 

  76. Meyer OA, Tilson HA, Byrd WC, Riley MT. A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehav Toxicol 1979; 1: 233–6.

    PubMed  CAS  Google Scholar 

  77. Maurissen JP, Marable BR, Andrus AK, Stebbins KE. Factors affecting grip strength testing. Neurotoxicol Teratol 2003; 25:543–53.

    Article  PubMed  CAS  Google Scholar 

  78. Freitag S, Schachner M, Morellini F. Behavioral alterations in mice deficient for the extracellular matrix glycoprotein tenascin-R. Behav Brain Res 2003; 145:189–207.

    Article  PubMed  CAS  Google Scholar 

  79. Karl T, Pabst R, von Horsten S. Behavioral phenotyping of mice in pharmacological and toxicological research. Exp Toxicol Pathol 2003; 55:69–83.

    Article  PubMed  Google Scholar 

  80. Sawada I, Kitahara M Yazawa Y. Swimming test for evaluating vestibular function in Guinea Pigs. Acta Otolaryngol. (Stokh) 1994; Suppl 510:20–3.

    Article  CAS  Google Scholar 

  81. Carter RJ, Morton AJ, Dunnet SB. Motor coordination and balance in rodents. In: Crawley JN, Gerfen CR, Rogawski MA, Sibley DR, Skolnick P, Wray S (eds), Current Protocols in Neuroscience 2001. John Wiley & Sons, Inc., New York, unit 8.12. pp. 1–14.

    Google Scholar 

  82. McFadyen MP, Kusek G, Bolivar VJ, Flaherty L. Differences among eight inbred strains of mice in motor ability and motor learning on a rotorod. Genes Brain Behav 2003; 2:214–9.

    Article  PubMed  CAS  Google Scholar 

  83. Brooks SP, Pask T, Jones L, Dunnett SB. Behavioural profiles of inbred mouse strains used as transgenic backgrounds. I: motor tests. Genes Brain Behav 2004; 3:206–15.

    Article  CAS  Google Scholar 

  84. Baird AL, Meldrum A and Dunnett SB. The staircase test of skilled reaching in mice. Brain Res Bull 2001; 54:243–50

    Article  PubMed  CAS  Google Scholar 

  85. Rácz I, Zimmer A. Animals Models of Nociception. In: Hrabé de Angelis M, Chambon P, Brown S (eds), Standards of Mouse Model Phenotyping 2006. Wiley-VCH, Weinheim, pp. 221–235.

    Chapter  Google Scholar 

  86. Johnson GJ, Foster A. Prevalence, incidence and distribution of visual impairment. In: The Epidemiology of Eye Disease 2004 (eds.: Johnson GJ, Minassian DC, Weale RA, West SK). Arnold, London UK, pp. 3–28.

    Google Scholar 

  87. Dalke C, Graw J. Mouse mutants as models for congenital retinal disorders. Exp Eye Res 2005; 81:503–12.

    Article  PubMed  CAS  Google Scholar 

  88. Graw J. The genetic and molecular basis of congenital eye defects. Nat Rev Genet 2003; 4:876–88.

    Article  PubMed  CAS  Google Scholar 

  89. Favor J. A comparison of the dominant cataract and recessive specific-locus mutation rates induced by treatment of male mice with ethylnitrosourea. Mutat Res 1983; 110:367–82.

    PubMed  CAS  Google Scholar 

  90. Hawes NL, Smith RS, Chang B, Davisson M, Heckenlively JR, John SW. Mouse fundus photography and angiography: A catalogue of normal and mutant phenotypes. Mol Vis 1999; 5:22.

    PubMed  CAS  Google Scholar 

  91. Aleman TS, Jacobson SG, Chico JD, et al. Impairment of the transient pupillary light reflex in Rpe65(–/–) mice and humans with leber congenital amaurosis. Invest Ophthalmos Vis Sci 2004; 45:1259–71.

    Article  Google Scholar 

  92. Schmucker C, Schaeffel F. In vivo biometry in the mouse eye with low coherence interferometry. Vision Res 2004; 44:2445–56.

    Article  PubMed  Google Scholar 

  93. Puk O, Dalke C, Favor J, Hrabé de Angelis M, Graw J. Variations of eye size parameters among different strains of mice. Mamm Genome 2006; 17:851–57.

    Article  PubMed  Google Scholar 

  94. Dalke C, Löster J, Fuchs H, et al. Electroretinography as a screening method for mutations causing retinal dysfunction in mice. Invest Ophthalmos Vis Sci 2004; 45:601–9.

    Article  Google Scholar 

  95. Thaung C, Arnold K, Jackson IJ and Coffey PJ. Presence of visual head tracking differentiates normal sighted from retinal degenerate mice. Neurosci Lett 2002; 325:21–4.

    Article  PubMed  CAS  Google Scholar 

  96. Douglas RM, Alam NM, Silver BD, McGill TJ, Tschetter WW, Prusky GT. Independent visual threshold measurements in the two eyes of freely moving rats and mice using a virtual-reality optokinetic system. Vis Neurosci 2005; 22:677–84.

    PubMed  CAS  Google Scholar 

  97. Schmucker C, Seeliger M, Humphries P, Biel M, Schaeffel F. Grating acuity at different luminances in wild-type mice and in mice lacking rod or cone function. Invest Ophthalmos Vis Sci 2005; 46:398–407.

    Article  Google Scholar 

  98. Rathkolb B, Decker T, Fuchs E, et al. The clinical–chemical screen in the Munich ENU Mouse Mutagenesis Project: screening for clinically relevant phenotypes. Mamm Genome 2000; 11:543–6.

    Article  PubMed  CAS  Google Scholar 

  99. Aigner B, Rathkolb B, Herbach N, et al. Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models. Am J Physiol – Renal Physiol 2007; 292:F1560–7.

    Article  CAS  Google Scholar 

  100. Herbach N, Rathkolb B, Kemter E, et al. Dominant-negative effects of a novel mutated Ins2 allele causes early-onset diabetes and severe beta-cell loss in Munich Ins2C95S mutant mice. Diabetes 2007; 56:1268–76.

    Article  PubMed  CAS  Google Scholar 

  101. Loeb WF, Quimby FW. The Clinical Chemistry of Laboratory Animals. Taylor & Francis, 1999, Philadelphia.

    Google Scholar 

  102. Klempt M, Rathkolb B, Aigner B, Wolf E. Clinical chemical screen. In: Hrabé de Angelis M, Chambon P, Brown S (eds), Standards of Mouse Model Phenotyping 2006, pp. 87–107. Wiley-VCH, Weinheim.

    Chapter  Google Scholar 

  103. Hough TA, Nolan P, Tsipouri V, et al. Novel phenotypes identified by plasma biochemical screening in the mouse. Mamm Genome 2002; 13:595–602.

    Article  PubMed  CAS  Google Scholar 

  104. Klempt M, Rathkolb B, Fuchs E, Hrabé de Angelis M, Wolf E, Aigner B. Genotype-specific environmental impact on the variance of blood values in inbred and F1 hybrid mice. Mamm Genome 2006; 17:93–102.

    Article  PubMed  Google Scholar 

  105. Rathkolb B, Tran TV, Klempt M, et al. Large scale albuminuria screen for nephropathy models in chemically induced mouse mutants. Nephron Exp Nephrol 2005; 100:e143–9.

    Article  PubMed  Google Scholar 

  106. Chen J. and D.E. Harrison. Quantitative trait loci regulating relative lymphocyte proportions in mouse peripheral blood. Blood 2002; 99:561–6.

    Article  PubMed  CAS  Google Scholar 

  107. Yellon SM, Tran LT. Photoperiod, reproduction, and immunity in selected strains of inbred mice. J Biol Rhythms 2002; 17:65–75.

    Article  PubMed  CAS  Google Scholar 

  108. Freitas AA, Rocha B. Population biology of lymphocytes. The Flight for survival. Annu Rev Immunol 2000; 18:83–111.

    Article  PubMed  CAS  Google Scholar 

  109. Grewal IS, Heilig M, Miller A, Sercarz EE. Environmental regulation of T-cell function in mice: group housing of males affects accessory cell function. Immunology 1997; 90:165–8.

    Article  PubMed  CAS  Google Scholar 

  110. Krzych U, Strausser HR, Bressler JP, Goldstein AL. Quantitative differences in immune responses during the various stages of the estrous cycle in female BALB/c mice. J Immunol 1978,121:1603–5.

    PubMed  CAS  Google Scholar 

  111. Weaver JL, Broud DD. Serial phenotypical analysis of mouse peripheral blood leukocytes. Toxicol Mech Methods 2002; 12:95–118.

    Article  PubMed  CAS  Google Scholar 

  112. Stevens TL, Bossie A, Sanders VM, et al. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature 1988; 334:255–8

    Article  PubMed  CAS  Google Scholar 

  113. Sant'Anna OA, Mouton D, Ibanez OM, et al. Basal immunoglobulin serum concentration and isotype distribution in relation to the polygenic control of antibody responsiveness in mice. Immunogenetics 1985; 22:131–9.

    Article  PubMed  Google Scholar 

  114. Fulton RJ, McDade RL, Smith PL, Kienker LJ, Kettman JR, Jr. Advanced multiplexed analysis with the FlowMetrix system. Clin Chem 1997; 43:1749–56.

    PubMed  CAS  Google Scholar 

  115. Godfrey DI, Kennedy J, Suda T, Zlotnik A. A developmental pathway involving four phenotypically and fuctionally distinct subsets of CD3-CD4-CD8-Triple negative adult mouse thymocytes defined by CD44 and CD25 expression. JI 1993; 150:4244–52

    CAS  Google Scholar 

  116. Tung JW, Parks DR, Moore WA, Herzenberg LA. Identification of B-cell subsets. Methods Mol Biol 2004; 271:37–58.

    PubMed  Google Scholar 

  117. Wong P, and EG Pamer. Feedback regulation of pathogen-specific T cell priming. Immunity 2003; 18:499–511.

    Article  PubMed  CAS  Google Scholar 

  118. Busch D H, and E G Pamer. T lymphocyte dynamics during Listeria monocytogenes infection. Immunol Lett 1999; 65:93–8.

    Article  PubMed  CAS  Google Scholar 

  119. Busch DH, I M Pilip, SVijh, and EG Pamer. Coordinate regulation of complex T cell populations responding to bacterial infection. Immunity 1998; 8:353–62.

    Article  PubMed  CAS  Google Scholar 

  120. Huster, KM, V Busch, M Schiemann, et al. Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets. Proc Natl Acad Sci USA 2004; 101:5610–5.

    Article  PubMed  CAS  Google Scholar 

  121. Baumgarth N, and M Roederer. A practical approach to multicolor flow cytometry for immunophenotyping. J Immunol Methods 2000; 243:77–97.

    Article  PubMed  CAS  Google Scholar 

  122. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002; 347:911–20.

    Article  PubMed  Google Scholar 

  123. McCunney RJ. Asthma, genes, and air pollution. J Occup Environ Med 2005; 47: 1285–91.

    Article  PubMed  CAS  Google Scholar 

  124. Wahn U, von Mutius E, Lau S, Nickel R. The development of atopic phenotypes: genetic and environmental determinants. Nestle Nutr Workshop Ser Pediatr Program 2007; 59:1–11; discussion 11–15.

    PubMed  Google Scholar 

  125. Jakob T, Köllisch GV, Howaldt M. et al. Novel mouse mutants with primary cellular immunodeficiencies generated by genome-wide mutagenesis. J Allergy Clin Immunol 2008; 121:179–84

    Article  PubMed  CAS  Google Scholar 

  126. Jakob T., Alessandrini F, Gutermuth J, et al. Phenotyping allergy in the laboratory mouse. In: Hrabé de Angelis M, Chambon P, Brown S (eds), Standards of Mouse Model Phenotyping 2006 Wiley-VCH, Weinheim, pp. 253–81

    Chapter  Google Scholar 

  127. Bauer R, Scheiblhofer S, Kern K, et al. Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive and therapeutic effects in a mouse model of allergy. J Allergy Clin Immunol 2006; 118:269–76.

    Article  PubMed  CAS  Google Scholar 

  128. Lommatzsch M, Julius P, Kuepper M et al. The course of allergen-induced leukocyte infiltration in human and experimental asthma. J Allergy Clin Immunol 2006; 118:91–7.

    Article  PubMed  CAS  Google Scholar 

  129. Klenerman P, Cerundolo V, Dunbar PR. Tracking T cells with tetramers: new tales from new tools. Nat Rev Immunol 2002; 2:263–72.

    Article  PubMed  CAS  Google Scholar 

  130. Miyahara N, Swanson BJ, Takeda K, et al. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nat Med 2004; 10:865–9.

    Article  PubMed  CAS  Google Scholar 

  131. McCusker CT. Use of mouse models of allergic rhinitis to study the upper and lower airway link. Curr Opin Allergy Clin Immunol 2004; 4:11–6.

    Article  PubMed  Google Scholar 

  132. Gutermuth J, Ollert M, Ring J, Behrendt H, Jakob T. Mouse models of atopic eczema critically evaluated. Int Arch Allergy Immunol 2004; 135:262–76.

    Article  PubMed  Google Scholar 

  133. Dearman RJ, Kimber I. A mouse model for food allergy using intraperitoneal sensitization. Methods 2007; 41:91–8.

    Article  PubMed  CAS  Google Scholar 

  134. Shinagawa K, Kojima M. Mouse model of airway remodeling: strain differences. Am J Respir Crit Care Med 2003; 168:959–67.

    Article  PubMed  Google Scholar 

  135. Melgert BN, Postma DS, Kuipers I, et al. Female mice are more susceptible to the development of allergic airway inflammation than male mice. Clin Exp Allergy 2005; 35:1496–1503.

    Article  PubMed  CAS  Google Scholar 

  136. Mayuzumi H, Ohki Y, Tokuyama K, et al. Age-related difference in the persistency of allergic airway inflammation and bronchial hyperresponsiveness in a murine model of asthma. Int Arch Allergy Immunol 2007; 143:255–62.

    Article  PubMed  CAS  Google Scholar 

  137. Bansal N, Houle A, Melnykovych G. Apoptosis: mode of cell death induced in T cell leukemia lines by dexamethasone and other agents. FASEB J 1991; 5:211–6.

    PubMed  CAS  Google Scholar 

  138. Jerome CP. Hormonal therapies and osteoporosis. Ilar J 2004; 45:170–8.

    PubMed  CAS  Google Scholar 

  139. Chowen JA, Azcoitia I, Cardona-Gomez GP, Garcia-Segura LM. Sex steroids and the brain: lessons from animal studies. J Pediatr Endocrinol Metab 2000; 13:1045–66.

    Article  PubMed  CAS  Google Scholar 

  140. Geissler WM, Davis DL, Wu L, et al. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet 1994; 7:34–9.

    Article  PubMed  CAS  Google Scholar 

  141. Mindnich R, Adamski J. Functional aspects of 17beta-hydroxysteroid dehydrogenase 1 determined by comparison to a closely related retinol dehydrogenase. J Steroid Biochem Mol Biol 2007; 104:334–9.

    Article  PubMed  CAS  Google Scholar 

  142. Möller G, Adamski J. Multifunctionality of human 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 2006; 248:47–55.

    Article  CAS  Google Scholar 

  143. Herman GE. Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes. Hum Mol Genet 2003; 12 Spec No 1:R75–88.

    Article  PubMed  CAS  Google Scholar 

  144. Prehn C, Ströhle F, Haller F, et al. A comparison of methods for assays of steroidogenic enzymes: new GC/MS versus HPLC and TLC. In: Enzymology and Molecular Biology of Carbonyl Metabolism, eds. In Weiner H, Plapp B, Lindhal R, Maser E (eds), pp 277–283, Purdue University Press, 2007, West Lafayette, Indiana, USA.

    Google Scholar 

  145. Sorensen KD, Kunder S, Quintanilla-Martinez L, Sorensen J, Schmidt J, Pedersen FS. Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage. Virology 2007; 362:179–91.

    Article  PubMed  CAS  Google Scholar 

  146. Favor J, Gloeckner CJ, Janik D, et al. Type IV procollagen missense mutations associated with defects of the eye, vascular stability, the brain, kidney function and embryonic or postnatal viability in the mouse, mus musculus: an extension of the Col4a1 allelic series and the identification of the first two Col4a2 mutant alleles. Genetics 2007; 175:725–36.

    Article  PubMed  CAS  Google Scholar 

  147. Wilson I, Gamble M. The hematoxylins and eosin. In: Theory and Practice of Histological Techniques 5th Edition (2000, reprint 2006), eds. Bancroft, J.D. and Gamble, M., Churchill Livingstone, Edinburgh, London, New York, Oxford, Philadelphia, St. Louis, Sydney, Toronto.

    Google Scholar 

  148. Bancroft JD, Gamble M. Theory and Practice of Histological Techniques 5th Edition, eds. Bancroft, J.D. and Gamble, M., Churchill Livingstone, 2002, Edinburgh

    Google Scholar 

  149. Toyota E, Kawaguchi Y, Ogasawara Y, et al. Novel rat model of ischemic cardiomyopathy induced by repetitive myocardial ischemia/reperfusion injury while conscious. Circ J 2007; 71:788–95.

    Article  PubMed  Google Scholar 

  150. Kwok-Kee C, Lowe J. Techniques in Neuropathology in Theory and Practice of Histological Techniques 5th Edition, eds. Bancroft, J.D. and Gamble, M., Churchill Livingstone, 2002, Edinburgh.

    Google Scholar 

  151. Jones LM. Lipids in Theory and Practice of Histological Techniques 5th Edition, eds. Bancroft, J.D. and Gamble, M., Churchill Livingstone, 2002, Edinburgh.

    Google Scholar 

  152. Kunder S, Calzada-Wack J, Hölzlwimmer G, et al. A Comprehensive Antibody Panel for Immunohistochemical Analysis of Formalin-fixed, Paraffin-embedded Hematopoietic Neoplasms of Mice. Analysis of mouse specific and human antibodies cross-reactive with murine tissue. Toxicol Pathol 2007; 35:366–75.

    Article  PubMed  CAS  Google Scholar 

  153. Kremer M, Quintanilla-Martínez L, Nährig J, von Schilling C, Fend F. Immunohistochemistry in bone marrow pathology: a useful adjunct for morphologic diagnosis Virchows Arch 2005; 447:920–37.

    Article  PubMed  Google Scholar 

  154. Otha Y, Ichimura K. Proliferation markers, proliferating cell nuclear antigen, Ki67, 5-bromo-2′-deoxyuridine, and cyclin D1 in mouse olfactory epithelium. Ann Otol Rhinol Laryngol 2000; 109:1046–8.

    Google Scholar 

  155. Vyas D, Robertson CM, Stromberg PE, et al. Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine. Histol Histopathol 2007; 22:623–30.

    PubMed  CAS  Google Scholar 

  156. Skalicky SE, Ow K, Hannan M, Russell PJ, Crowe PJ, Yang JL. P53 expression is associated with malignant potential in xenograft tissues of a fibrosarcoma mouse model. Anticancer Res 2007; 27:973–8.

    PubMed  CAS  Google Scholar 

  157. Galeano B, Klootwijk R, Manoli I, et al. Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine. J Clin Invest 2007; 117:1585–94.

    Article  PubMed  CAS  Google Scholar 

  158. Stirling JW, Coleman M, Thomas A, Woods AE. Role of transmission electron microscopy in tissue diagnosis: Diseases of the kidney, skeletal muscle and myocardium. J Cell Pathol 1999; 4: 223–43.

    Google Scholar 

  159. Qiao B, Wu J, Chu YW, et al. Induction of systemic lupus erythematosus-like syndrome in syngenic mice by immunization with activated lymphocyte-derived DNA. Rheumatology 2005; 44:1108–14.

    Article  PubMed  CAS  Google Scholar 

  160. Potter SS, Hartman HA, Kwan KM, Behringer RR Patterson LT. Laser Capture-Microarray Analysis of Lim1 Mutant Kidney Development. Genesis 2007; 45:432–9.

    Article  PubMed  CAS  Google Scholar 

  161. Anon. Mutant mice galore. Nature 2007; 446:469–70

    Google Scholar 

  162. Cardiff RD. Pathologists needed to cope with mutant mice. Nature 2007; 447:528

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This work was supported by NGFNplus grants from the Bundesministerium für Bildung und Forschung (01GS0850, 01GS0851, 01GS0852, 01GS0868, 01GS0869, 01GS0854) and by an EU grant (LSHG-2006-037188).

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Gailus-Durner*, V. et al. (2009). Systemic First-Line Phenotyping. In: Wurst, W., Kühn, R. (eds) Gene Knockout Protocols. Methods in Molecular Biology, vol 530. Humana Press. https://doi.org/10.1007/978-1-59745-471-1_25

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