Gestation interval, age at maturity and life span vary proportionally across mammalian species. This intriguing observation is the basis for the hypothesis that a set of master clocks exists, which determines rates of transition through different life cycle stages. Interspecies comparisons, however, do not allow a direct genetic analysis of determinants of timing because mammalian species generally do not interbreed. We have recently characterized a number of mouse strains whose ages of the onset of reproduction are drastically different. Two interstrain crosses between the slowest and fastest developing strains will be produced and for each individual timing of sexual maturation and several other developmental milestones will be evaluated. We will then test the hypothesis that a single or a few QTL(s) exist(s) with a large effect on timing of the onset of reproduction. In the second part of the proposal we will produce another two crosses between strains which have been shown to have different alleles increasing maximal life span. In these two crosses we will also look for QTLs affecting developmental timing and will test the hypothesis that some QTLs that affect timing of sexual maturation superimpose with QTLs affecting aging, suggesting the existence of genes with pleiotropic effects on development and aging.
| Klebanov, S; Harrison, D E (2002) Optimizing detection of QTLs retarding aging: choice of statistical model and animal requirements. Mech Ageing Dev 123:131-44 |
| Klebanov, S; Astle, C M; Roderick, T H et al. (2001) Maximum life spans in mice are extended by wild strain alleles. Exp Biol Med (Maywood) 226:854-9 |
| Klebanov, S; Flurkey, K; Roderick, T H et al. (2000) Heritability of life span in mice and its implication for direct and indirect selection for longevity. Genetica 110:209-18 |
