International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Johnson DK 1, Miller DR 1, Moustaid-Moussa N 2, Goldowitz D 3

1 Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, United States, 2 Dept. of Nutrition, University of Tennessee, Knoxville, United States, 3 Dept. of Anatomy and Neurobiology, University of Tennessee Health Sciences Center, Memphis, United States

With the goal of discovering genes that extend the healthy life span in mammals, we are phenotyping mice carrying new mutations induced by N-ethyl-N-nitrosourea (ENU).  The phenotyping plan includes evaluation for markers of growth trajectory and stress response in pedigrees aged to 28 months and beyond.

For the aging core, four males and four females of the “test class” are group-housed at

weaning to await screening at 18 months for behavioral and neuroanatomical abnormalities and at 19-24 months for factors thought to be predictive of longevity. Mice of the genotype that is homozygous for a mutagenized G0 grandparental target chromosome constitute the “test class” that should manifest any obvious or subtle abnormal recessive phenotypes caused by a new ENU-induced mutation.  This test class can be identified by visual or molecular markers.

To date, we have aged 202 pedigrees beyond 18 months and screened for body weight, blood glucose, leptin, insulin, insulin-like growth factor-1, corticosterone, and ability to maintain body temperature in the cold. We have identified phenodeviants for early low and high body weight, high corticosterone, high and low blood glucose, high core temperature, high IGF-1, high IGF-1 + high insulin, low core temperature + low IGF-1, and low leptin.  We are also developing software-analysis tools for determining bone density and body-fat content from microCT images. Phenodeviant pedigrees are being recovered for confirmation of heritability of the ascertained phenotype by breeding old males or by performing intracytoplasmic sperm injection using sperm routinely frozen from young males.

This work is supported by the National Institute on Aging in grant U01 MH61971 to the Tennessee Mouse Genome Consortium.

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