Genetic analysis of lifespan in hybrid progeny derived from the SAMP1 mouse strain with accelerated senescence

The SAMP1 mouse, a senescence-accelerated mouse prone (SAMP) strain, shows accelerated senescence coupled with a short lifespan as a genetic trait, an d has been used in gerontological research. The accelerated senescence and short lifespan of SAMP strains is considered to be under the control of mul tiple genes. To identify the chromosomal regions encompassing the genes for the accelerated senescence and short lifespan, we performed whole genome s canning with polymorphic marker loci in a progeny from a cross between the SAMP1 strain and normal B10.BR strain. A genetically recessive effect of th e amyloidogenic Apoa2(c) allele from SAMP1 on chromosome 1 to shorten the l ifespan was demonstrated in the progeny, consistent with the previous repor t. The recessive effect was observed also at D1Mit67, D5Mit267, D6Mit384 an d D19Mit33, suggesting the presence of genes for accelerated senescence in the SAMP strains around these loci. Other markers on chromosomes 8, 14, 16, and 17, however, exhibited a dominant or additive effect to shorten or pro long the lifespan, demonstrating a complex genetic control of the trait. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.