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Detecting Novel Bone Density and Bone Size Quantitative Trait Loci Using a Cross of MRL/MpJ and CAST/EiJ Inbred Mice

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Abstract

Most previous studies to identify loci involved in bone mineral density (BMD) regulation have used inbred strains with high and low BMD in generating F2 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 × CAST F2 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 × 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.

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Acknowledgements

This work was supported by Assistance Award DAMD17-99-1-9571. The U.S. Army Medical Research Acquisition Activity is the awarding and administering acquisition office. The information contained in this publication does not necessarily reflect the position or policy of the government, and no official endorsement should be inferred. The authors thank Courtney Kruse for technical assistance and the staff of the Jerry L. Pettis Memorial VA Medical Center, where this work was performed, for their support.

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Authors and Affiliations

  1. Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, 11201 Benton Street, Loma Linda, CA, 92357, USA

    H. Yu, S. Mohan, B. Edderkaoui, G. L. Masinde, H. M. Davidson & J. E. Wergedal

  2. Department of Biochemistry, Loma Linda University, 11234 Anderson Street, Loma Linda, CA, 92354, USA

    S. Mohan & J. E. Wergedal

  3. Department of Medicine, Loma Linda University, 11234 Anderson Street, Loma Linda, CA, 92354, USA

    S. Mohan, J. E. Wergedal & D. J. Baylink

  4. The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA

    W. G. Beamer

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  1. H. Yu
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  2. S. Mohan
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  3. B. Edderkaoui
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  4. G. L. Masinde
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  5. H. M. Davidson
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  6. J. E. Wergedal
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  7. W. G. Beamer
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  8. D. J. Baylink
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Correspondence to S. Mohan.

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Yu, H., Mohan, S., Edderkaoui, B. et al. Detecting Novel Bone Density and Bone Size Quantitative Trait Loci Using a Cross of MRL/MpJ and CAST/EiJ Inbred Mice. Calcif Tissue Int 80, 103–110 (2007). https://doi.org/10.1007/s00223-006-0187-z

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  • DOI: https://doi.org/10.1007/s00223-006-0187-z

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