Talk 11
Presenter: Cheryl Ackert-Bicknell
Thursday, 9:30am

Identification of Slc9a9 as a candidate gene for a bone mineral density QTL on mouse chromosome 9

Cheryl L. Ackert-Bicknell, Dana A. Godfrey, Rong Yuan, Gary A. Churchill, Kwangbom Choi, Matthew A. Hibbs and Daniel M. Gatti
1The Jackson Laboratory, Bar Harbor, Maine, USA 2Department of Internal Medicine, Southern Illinois University School of Medicine, Carbondale, Illinois, USA 3Trinity University, San Antonio, Texas, USA

Bone mineral density (BMD) is a strong predictor of osteoporotic fracture risk and over 80% of the variance in peak bone mass is due to heritable factors. In this study, 588 mice from a reciprocal cross between KK/HlJ and PL/J were phenotyped for whole body areal BMD by dual X-ray absorptiometry at 16 weeks of age. Using standard techniques QTL for this phenotype were mapped and 8 highly significant loci were identified, including a locus with a peak at 45.3 cM on Chromosome 9. Loci for BMD had previously been identified in other crosses in this region including: MRL×SJL (42.3 cM), B6×C3H (44.24 cM) and NZB×SM (46.08 cM). The boundaries of these overlapping QTL were used to define the most likely genomic interval to contain the underlying gene(s). The alleles for SNP in this interval were examined to identify genes wherein all strains contributing the high BMD allele for the QTL shared the same SNP allele and vice versa. Only three SNP within the interval met this allele distribution pattern and all were found within the Slc9a9 gene. This gene codes for one of the many solute transporter transmembrane proteins, but little is know about the function of this gene in particular. The Slc9a9 gene shows abundant expression in osteoblasts, the cell responsible for bone formation and across osteoblastogenesis, expression of this gene increases sharply coincident with mineralization. In sum, Slc9a9 is a strong candidate for a BMD QTL on mouse chromosome 9 and may be associated with osteoblast function.