Zhang QianKun, Cho Kyu-Hyuk, Cho Jae-Woo, Cha Dal-Sun, Park Han-Jin, Yoon Seokjoo, Zhang ShouFa, Song Chang-Woo
110Department of Research & Development, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, P.O BOX 123, Yuseong, Daejeon, 305-343 Korea.
210Department of Veterinary Medicine, YanBian University, Longjing, China.
Toxicol Res. 2008 Mar;24(1):69-78. doi: 10.5487/TR.2008.24.1.069. Epub 2008 Mar 1.
Mutant mouse which show dwarfism has been developed by -ethyl--nitrosourea (ENU) mutagenesis using BALB/c mice. The mutant mouse was inherited as autosomal recessive trait and named Small Body Size (SBS) mouse. The phenotype of SBS mouse was not apparent at birth, but it was possible to distinguish mutant phenotype from normal mice 1 week after birth. In this study, we examined body weight changes and bone mineral density (BMD), and we also carried out genetic linkage analysis to map the causative gene(s) of SBS mouse. Body weight changes were observed from birth to 14 weeks of age in both affected (n = 30) and normal mice (n = 24). BMD was examined in each five SBS and normal mice between 3 and 6 weeks of age, respectively. For the linkage analysis, we produced backcross progeny [(SBS × C57BL/6J) F × SBS] N mice (n = 142), and seventy-four microsatellite markers were used for primary linkage analysis. Body weight of affected mice was consistently lower than that of the normal mice, and was 43.7% less than that of normal mice at 3 weeks of age ( < 0.001). As compared with normal mice at 3 and 6 weeks of age, BMD of the SBS mice was significantly low. The results showed 15.5% and 14.1% lower in total body BMD, 15.3% and 8.7% lower in forearm BMD, and 29.7% and 20.1% lower in femur BMD, respectively. The causative gene was mapped on chromosome 10. The map order and the distance between markers were - 2.1 cM - - 4.2 cM - - 0.7 cM - - 1.4 cM - - 11.2 cM - .
通过使用BALB/c小鼠进行N-乙基-N-亚硝基脲(ENU)诱变,培育出了表现出侏儒症的突变小鼠。该突变小鼠作为常染色体隐性性状遗传,被命名为小体型(SBS)小鼠。SBS小鼠的表型在出生时并不明显,但在出生1周后就有可能将突变表型与正常小鼠区分开来。在本研究中,我们检测了体重变化和骨矿物质密度(BMD),并且还进行了基因连锁分析以定位SBS小鼠的致病基因。在受影响的小鼠(n = 30)和正常小鼠(n = 24)中观察了从出生到14周龄的体重变化。分别在3至6周龄的每组五只SBS小鼠和正常小鼠中检测了BMD。为了进行连锁分析,我们产生了回交后代[(SBS×C57BL/6J)F1×SBS]N小鼠(n = 142),并且使用74个微卫星标记进行了初步连锁分析。受影响小鼠的体重始终低于正常小鼠,在3周龄时比正常小鼠低43.7%(P < 0.001)。与3周龄和6周龄的正常小鼠相比,SBS小鼠的BMD显著较低。结果显示,全身BMD分别低15.5%和14.1%,前臂BMD分别低15.3%和8.7%,股骨BMD分别低29.7%和20.1%。致病基因被定位在10号染色体上。标记之间的图谱顺序和距离为 - 2.1厘摩 - - 4.2厘摩 - - 0.7厘摩 - - 1.4厘摩 - - 11.2厘摩 - 。