Molecular Genetic Analysis of Senescence-Accelerated Mouse (SAM)

1)SAM小鼠加速衰老和年龄相关性疾病的遗传学分析：1)我们观察到两个染色体区域(Chr.5和7)导致SAMP1小鼠加速衰老，寿命比对照品系小鼠短。2)建立了导致SAMP6小鼠骨质疏松的三个染色体区域(PBD-1、2、3)的SAMP6小鼠与正常SAMP2小鼠之间的同源、亚同源和最终亚同源品系。我们比较了同种小鼠品系中PBD-2关键区域基因的表达水平，发现SAMP6小鼠骨骼中Sfr4(Wint蛋白的诱饵受体)的表达是SAMP2小鼠的10倍以上。我们现在提出的假设是，在SAMP6小鼠中，Sfr4的表达增加抑制了Wint的信号转导，并导致成骨细胞分化降低。3)我们使用易患淀粉样变性SA…进行了遗传分析较多的MP1小鼠和较少的淀粉样变性A/J小鼠，两者都具有淀粉样变性APOA2^c等位基因，以确定淀粉样变性的修饰基因。我们鉴定了两个染色体区域(Chr.2)基因表达系列分析(SAGE)揭示的小鼠睾丸转录组：我们用SAGE方法分析了年轻和老年SAMR1和SAMP1小鼠的基因表达谱。我们测定了19,000多个基因，发现少精子症特异性转录因子的减少导致了它们下游许多基因的减少。3)使用SAM菌株的协作工作：SAMP1小鼠的行为节律紊乱通过自发的车轮运动部分恢复正常。我们使用SAMP10小鼠品系和对照Samri品系进行遗传分析，以确定SAMP10品系中与年龄相关的学习障碍和脑萎缩相关的基因。我们正在与卡内卡公司和高知大学医学院合作，分析辅酶Q10和富含β-胡萝卜素的藻类的抗衰老作用。较少

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