Genetic study of learning and memory deficits in SAMP8 mice

Cross-mating between SAMP8 and JF1 (Japanese Fancy Mouse 1) normal mice was performed for the genetic studies. At 5 months of age, learning and memory deficits (LMD) of F2 and backcross progenies were assessed using a Step-Through passive avoidance apparatus. The F2 generation showed a 3:1 segregation ratio of LMD to normal mice, and the backcross generation segregated into a 1:1 ratio of LMD to normal mice. These results are in good agreement with Mendelian inheritance. Estimation of the number of genes using Wright's formula showed that at least two to three genes are involved in the development of LMD in SAMP8 mice. Thus, LMD in SAMP8 mice may be inherited by a relatively small number of genes and regulated by a major single gene. In further experiments, we conducted QTL analysis to identify memory dysfunction QTLs in SAMP8 mice using 264 F2 progenies. A total of 126 genetic markers were typed in all chromosomes. Four significant QTLs to LMD were identified on chromosomes 1, 12, 13, and 15. The number of these QTLs is almost consistent with the statistically estimated gene number. Congenic strains carrying the QTLs need to be produced to verify the existence of LMD genes in the candidate regions of the chromosomes.