Yu H, Mohan S, Edderkaoui B, Masinde G L, Davidson H M, Wergedal J E, Beamer W G, Baylink D J
Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, 11201 Benton Street, Loma Linda, CA 92357, USA.
Calcif Tissue Int. 2007 Feb;80(2):103-10. doi: 10.1007/s00223-006-0187-z. Epub 2007 Feb 2.
Most previous studies to identify loci involved in bone mineral density (BMD) regulation have used inbred strains with high and low BMD in generating F(2) mice. However, differences in BMD may not be a requirement in selecting parental strains for BMD quantitative trait loci (QTL) studies. In this study, we intended to identify novel QTL using a cross of two strains, MRL/MpJ (MRL) and CAST/EiJ (CAST), both of which exhibit relatively high BMD when compared to previously used strains. In addition, CAST was genetically distinct. We generated 328 MRL x CAST F(2) mice of both sexes and measured femur BMD and periosteal circumference (PC) using peripheral quantitative computed tomography. Whole-genome genotyping was performed with 86 microsatellite markers. A new BMD QTL on chromosome 10 and another suggestive one on chromosome 15 were identified. A significant femur PC QTL identified on chromosome 9 and a suggestive one on chromosome 2 were similar to those detected in MRL x SJL. QTL were also identified for other femur and forearm bone density and bone size phenotypes, some of which were colocalized within the same chromosomal positions as those for femur BMD and femur PC. This study demonstrates the utility of crosses involving inbred strains of mice which exhibit a similar phenotype in QTL identification.
以往大多数旨在鉴定参与骨密度（BMD）调节基因座的研究，在培育F2代小鼠时都使用了具有高、低BMD的近交系。然而，在选择用于BMD数量性状基因座（QTL）研究的亲本品系时，BMD差异可能并非必要条件。在本研究中，我们打算通过两个品系MRL/MpJ（MRL）和CAST/EiJ（CAST）的杂交来鉴定新的QTL，与之前使用的品系相比，这两个品系均表现出相对较高的BMD。此外，CAST在遗传上是独特的。我们培育了328只雌雄均有的MRL×CAST F2代小鼠，并使用外周定量计算机断层扫描测量了股骨BMD和骨膜周长（PC）。用86个微卫星标记进行了全基因组基因分型。在10号染色体上鉴定出一个新的BMD QTL，在15号染色体上鉴定出另一个提示性QTL。在9号染色体上鉴定出一个显著的股骨PC QTL，在2号染色体上鉴定出一个提示性QTL，与在MRL×SJL中检测到的相似。还鉴定出了其他股骨和前臂骨密度及骨大小表型的QTL，其中一些与股骨BMD和股骨PC的QTL共定位于相同的染色体位置。本研究证明了在QTL鉴定中涉及具有相似表型的近交系小鼠杂交的实用性。
