Molecular Genetic Analysis of Senescence-Accelerated Mouse (SAM)

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1)Genetic Analysis of Accelerated Senescence and Age-related Disorders in SAM mice : 1)We observed that the congenic mouse strains of the two chromosomal regions (Chr. 5 and 7) responsible for the accelerated senescence in SAMP1 mice, have shorter life span than the control strain mice. 2)We have made congenic, sub-congenic and finaly sub-subcongenic mouse strains between osteoporotic SAMP6 and normal SAMP2 mice of three chromosomal regions (Pbd-1, 2, 3) responsible for osteoporosis (low peak born mass) in SAMP6 mice. We compared the expression levels of genes in the "critical region of Pbd-2" among congenic mouse strains and found that Sfr4 (decoy receptor for Wint protein) is expressed more than 10 times higher in the bone of SAMP6 mice compared with SAMP2. We now propose the hypothesis that the increased expression of Sfr4 inhibit the signal transduction of Wint and lead to lower differentiation of osteoblast in SAMP6 mice. 3) We performed genetic analysis using amyloidosis prone SA … More MP1 mice and less amyloidogenic A/J mice, both of which have amyloidogenic Apoa2^c allele to determine the modifier genes of amyloidosis. We identified two chromosomal regions (Chr. 14, and 19) responsible for inhibition of amyloidosis.2)Mouse Testis Transcriptome Revealed Using Serial Analysis of Gene Expression (SAGE) : We assayed gene expression profiles (transcriptome) of young and old SAMR1 and SAMP1 mice using SAGE method. We determined over 19,000 genes and found that the reduction of oligozoospermia specific transcription factors lead to the reduction of many genes down stream of them.3)Collaborative Works Using SAM Strains : Diurnal rhythm disorder of behavioral activity in SAMP1 mice was partially normalized by spontaneous wheel running. We performed genetic analysis using SAMP10 mouse strain and control SAMRI strain to identify the genes responsible for age-related learning disability and brain atrophy in SAMP10 strain. We are collaboration with Kaneka Co and Kohchi University School of Medicine to analyze anti-aging effects of Coenzyme Q10 and beta-carotene rich Algae. Less