Abstract
With the goal of discovering genes that contribute to late-onset neurological and ocular disorders and also genes that extend the healthy life span in mammals, we are phenotyping mice carrying new mutations induced by the chemical N-ethyl-N-nitrosourea (ENU). The phenotyping plan includes basic behavioral, neurohistological, and vision testing in sibling cohorts of mice aged to 18 months, and then evaluation for markers of growth trajectory and stress response in these same cohorts aged up to 28 months. Statistical outliers are identified by comparison to test results of similar aged cohorts, and potential mutants are recovered for re-aging to confirm heritability of the phenotype.
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References
de Haan G and Williams RW (2005) A genetic and genomic approach to identify longevity genes in mice. Mech Ageing Dev 126: 82–92
Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P and Le Bouc Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182–186
Kawase Y, Iwata T, Toyoda Y, Wakayama T, Yanagimachi R and Suzuki H (2001) Comparison of intracytoplasmic sperm injection for inbred and hybrid mice. Mol Reprod Dev 60: 74–78
Kimura Y and Yanagimachi R (1999) Intracytoplasmic sperm injection in the mouse. Biol Reprod 52: 709–720
Martin AC, Thornton JD, Liu J, Wang XF, Zuo J, Jablonski MM, Chaum E, Zindy F and Skapek SX (2004) Pathogenesis of persistent hyperplastic primary vitreous in mice lacking the Arf tumor suppressor gene. Investig Ophthalmol Vis Sci 45: 3387–3396
Migliaciccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L and Pelicci PG (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402: 309–313
Napoli C, Martin-Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, Condorelli M, Sica G, De Rosa G and Pelicci P (2003) Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA 100: 2112–2116
Rinchik EM (2000) Developing genetic reagents to facilitate recovery, analysis, and maintenance of mouse mutations. Mamm Genome 11: 489–499
Russell WL, Kelly EM, Hunsicker PR, Bangham JW and Maddux SC (1979) Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc Natl Acad Sci USA 76: 5818–5819
Russell LB, Montgomery CS, Cacheiro NL and Johnson DK (1995) Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse. Genetics 141: 1547–1562
Semenova E, Wang XF, Jablonski MM, Levorse J and Tilghman SM (2003) An engineered 800 kilobase deletion of Uchl3 and Lmo7 on mouse chromosome 14 causes defects in viability, postnatal growth and degeneration of muscle and retina. Hum Mol Genet 12: 1301–1312
Szczygiel MA, Kusakabe H, Yanagimachi R and Whittingham DG (2002) Intracytoplasmic sperm injection is more efficient than in vitro fertilization for generating mouse embryos from cryopreserved spermatozoa. Biol Reprod 67: 1278–1284
The Complex Trait Consortium (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet 36: 1–4
Vogel G (2003) Scientists dream of 1001 complex mice. Science 301: 456–457
Williams RW (1999) A chromosome-specific recessive mutagenesis screen suitable for detecting mutations with subtle effects. Mamm Genome 10: 734–738
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Johnson, D.K., Rinchik, E.M., Moustaid-Moussa, N. et al. Phenotype screening for genetically determined age-onset disorders and increased longevity in ENU-mutagenized mice. AGE 27, 75–90 (2005). https://doi.org/10.1007/s11357-005-4131-3
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DOI: https://doi.org/10.1007/s11357-005-4131-3