Our preliminary study indicated that, in comparison to C57BL/6J mice, inbred BALB/cByJ mice have an age-associated primitive hemopoietic stem cell (PHSC) defect in which PHSC repopulating capability reduced dramatically in aged individuals. This project aimed to define the genetic factor(s) that causing this PHSC aging defect in BALB mice and to study the effects of PHSC aging on PHSC repopulation in vivo and proliferation and differentiation in vitro. By typing PHSC aging phenotype on (BALB x B6) Fl hybrids and on CXB recombinant inbred (RI) mice using the competitive repopulation assay, we will determine whether PHSC aging is a dominant, co-dominant or recessive trait and will estimate how many loci are important in controlling its phenotype. We will have a possibility to establish a phenotype.DNA marker linkage to localize potential locus or loci to a chromosomal segment if only l or 2 loci are important. Using bone marrow transplantation, we will test our hypothesis that PHSC aging defect progresses with age in BALB mice with reducing PHSC abilities to compete for repopulation. We will also test that PHSC aging will affect PHSC capabilities to proliferate and differentiate in vitro.
| 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 |
