Kataoka Taro, Tamura Masaru, Maeno Akiteru, Wakana Shigeharu, Shiroishi Toshihiko
Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
G3 (Bethesda). 2017 Oct 5;7(10):3449-3457. doi: 10.1534/g3.117.300213.
Trabecular bone structure has an important influence on bone strength, but little is known about its genetic regulation. To elucidate the genetic factor(s) regulating trabecular bone structure, we compared the trabecular bone structures of two genetically remote mouse strains, C57BL/6J and Japanese wild mouse-derived MSM/Ms. Phenotyping by X-ray micro-CT revealed that MSM/Ms has structurally more fragile trabecular bone than C57BL/6J. Toward identification of genetic determinants for the difference in fragility of trabecular bone between the two mouse strains, we employed phenotype screening of consomic mouse strains in which each C57BL/6J chromosome is substituted by its counterpart from MSM/Ms. The results showed that many chromosomes affect trabecular bone structure, and that the consomic strain B6-Chr15, carrying MSM/Ms-derived chromosome 15 (Chr15), has the lowest values for the parameters BV/TV, Tb.N, and Conn.D, and the highest values for the parameters Tb.Sp and SMI. Subsequent phenotyping of subconsomic strains for Chr15 mapped four novel trabecular bone structure-related QTL () on mouse Chr15. These results collectively indicate that genetic regulation of trabecular bone structure is highly complex, and that even in the single Chr15, the combined action of the four s controls the fragility of trabecular bone. Given that is syntenic to human Chr 12q12-13.3, where several bone-related SNPs are assigned, further study of should facilitate our understanding of the genetic regulation of bone formation in humans.
小梁骨结构对骨强度有重要影响，但其遗传调控却知之甚少。为了阐明调节小梁骨结构的遗传因素，我们比较了两种遗传关系较远的小鼠品系C57BL/6J和日本野生小鼠衍生的MSM/Ms的小梁骨结构。通过X射线显微CT进行表型分析发现，MSM/Ms的小梁骨在结构上比C57BL/6J更脆弱。为了确定这两种小鼠品系小梁骨脆弱性差异的遗传决定因素，我们对代换系小鼠品系进行了表型筛选，其中每个C57BL/6J染色体都被其对应的MSM/Ms染色体所取代。结果表明，许多染色体影响小梁骨结构，并且携带MSM/Ms来源的15号染色体（Chr15）的代换系B6-Chr15的骨体积分数（BV/TV）、骨小梁数量（Tb.N）和骨连接密度（Conn.D）参数值最低，而骨小梁间距（Tb.Sp）和结构模型指数（SMI）参数值最高。随后对Chr15的次代换系进行表型分析，在小鼠Chr15上定位了四个与小梁骨结构相关的新数量性状位点（QTL）。这些结果共同表明，小梁骨结构的遗传调控非常复杂，即使在单个Chr15中，这四个QTL的联合作用也控制着小梁骨的脆弱性。鉴于该区域与人类12q12 - 13.3染色体同线性，该区域已定位了几个与骨相关的单核苷酸多态性（SNP），对该区域的进一步研究应有助于我们理解人类骨形成的遗传调控。
