Hsu H-C, Zhang H-G, Li L, Yi N, Yang P-A, Wu Q, Zhou J, Sun S, Xu X, Yang X, Lu L, Van Zant G, Williams R W, Allison D B, Mountz J D
Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Genes Immun. 2003 Sep;4(6):402-10. doi: 10.1038/sj.gene.6363982.
A comprehensive analysis of initial thymus size and involution rate has not been quantitated for different genetic backgrounds of mice, thus genetic linkage analysis of thymic involution has not been possible. Here, we have used a mathematical method to analyze the age-related decline in thymocyte count in C57BL/6 and DBA/2 mice and have observed that thymic involution could be best fit with a negative exponential curve N(t)=beta(0) x exp(-beta(1)t), where t represents the age (day). This regression model was applied to C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice to identify the genetic loci influencing age-related thymic involution. There was a dramatic genetic effect of B and D alleles on thymocyte count at young age and the age-related thymic involution rate. The strongest quantitative trait loci (QTL) influencing the rate of thymic involution were mapped to mouse chromosome (Chr) 9 (D9Mit20 at 62 cM) and Chr 10 (D10Mit61 at 32 cM). The strongest QTLs influencing the initial thymocyte count were mapped to ChrX (DXMit324 at 26.5 cM) and Chr 3 (D3Mit127 at 70.3 cM). The present study suggests that the initial thymus size and the rate of thymic involution may be influenced by a relatively small number of genetic loci.
尚未对不同遗传背景的小鼠进行初始胸腺大小和退化率的综合定量分析，因此无法对胸腺退化进行遗传连锁分析。在此，我们使用一种数学方法分析了C57BL/6和DBA/2小鼠中胸腺细胞数量随年龄的下降情况，并观察到胸腺退化最适合用负指数曲线N(t)=beta(0) x exp(-beta(1)t)来拟合，其中t代表年龄（天）。将该回归模型应用于C57BL/6 x DBA/2（B x D）重组近交系小鼠，以确定影响年龄相关胸腺退化的基因座。B和D等位基因对幼年时的胸腺细胞数量和年龄相关的胸腺退化率有显著的遗传效应。影响胸腺退化率的最强数量性状基因座（QTL）被定位到小鼠染色体（Chr）9（62 cM处的D9Mit20）和Chr 10（32 cM处的D10Mit61）。影响初始胸腺细胞数量的最强QTL被定位到ChrX（26.5 cM处的DXMit324）和Chr 3（70.3 cM处的D3Mit127）。本研究表明，初始胸腺大小和胸腺退化率可能受相对较少数量的基因座影响。
