Animal Model of Brain Aging: Senescence-Accelerated Mouse (SAM)

Abstract

Senescence-accelerated mouse (SAM), a murine model of accelerated senescence, was established by Takeda et al. (59) at Kyoto University. In 1968, several pairs of the AKR/J strain of mice were donated by the Jackson Laboratory (Bar Harbor, ME) to the Department of Pathology (currently the Department of Senescence Biology), Chest Disease Research Institute (currently Institute for Frontier Medical Sciences), Kyoto University, Japan. While continuing sister-brother mating to maintain the inbred strain, researchers were aware that in certain litters most of the mice showed a moderate-to-severe degree of loss of activity, hair loss, lack of glossiness, skin coarseness, periophthalmic lesions, increased lordokyphosis, and early death. In 1975, five litters of mice with severe exhaustion were selected as the progenitors of the senescence-prone series (P series). Litters in which the aging process was normal were selected as progenitors of the senescence-resistant series (R series). Thereafter, selective breeding was based on the data of the grading score of senescence (16), life span, and pathogenic phenotypes in addition to the routine sister-brother mating (56,57,59). SAM consists of senescence-accelerated-prone mouse (SAMP) and senescence-accelerated-resistant mouse (SAMR), the latter of which shows normal aging characteristics. At present, there are 12 lines of SAM: nine SAMP substrains, including SAMP1, SAMP2, SAMP3, SAMP6, SAMP7, SAMP8, SAMP9, SAMP10, and SAMP11; and three SAMR substrains, including SAMR1, SAMR4, and SAMR5 (56). SAM strains manifest various phenotypes that are characteristic enough to differentiate the SAM strains (Table 1): senile amyloidosis in SAMP1, SAMP2, SAMP10, and SAMP11 (14,15,60); impaired immune response in SAMP1, SAMP2 (18,19), and SAMP8 (1); contracted kidney in SAMP1,