Bmd5a^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Bmd5a^C3H/HeJ
• Name: bone mineral density 5a; C3H/HeJ
• MGI ID: MGI:3830037
• QTL: Bmd5a Location: Chr1:173195927-173336154 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers decreased vBMD and cortical thickness in males and increased vBMD, cortical thickness and BV/TV in females compared to C57BL/6J. (J:139423)

Expression

In Structures Affected by this Mutation:

2 anatomical structure(s)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:139423

A series of nested subcongenic strains derived from C3H/HeJ donor DNA at the Bmd5 locus on a C57BL/6J genetic background was used to refine the QTL into three separate regions named Bmd5a, Bmd5b and Bmd5c. Bmd5 (bone mineral density 5) previously mapped to 81.6 cM on mouse Chromosome 1 and appears cover a broad area containing more than one QTL. Parental strain C3H/HeJ displays increased femoral bone mineral density compared to parental strain C57BL/6J. The phenotype also appears to be dependent on sex as females from C3H/HeJ and C57BL/6J display different bone traits compared to males from C3H/HeJ and C57BL/6J. Animals were sacrificed and phenotyped for femur BMD and trabecular thickness at 16 weeks of age.

Bmd5a (bone mineral density 5a) is correlatedwith marker D1Mit355 (97 cM; 175.335 Mb) and the QTL interval is flanked by rs30595455 (175.298 Mb) and rs6197487 (175.438 Mb). C3H/HeJ-derived alleles atBmd5a confer decreased vBMD and cortical thickness in males while increasing vBMD, cortical thicknessand BV/TV in females. Potential candidate genes for Bmd5a are Aim2 (formerly Gm1313; 175.28 Mb) and the predicted gene EG240921 (175.39 Mb).

Bmd5b (bone mineral density 5b) is flanked by D1Mit111 (92.3 cM; 170.937 Mb) and rs3710340 (173.868 Mb). Males fromtwo congenic sublines carrying Bmd5b displayed increased trabecular thickness while males from two congenic sublines carrying Bmd5b displayed increased trabecular thickness; however, all congenic sublines with C3H/HeJ-derived DNA at Bmd5b had increasedBV/TB. The Bmd5b interval contains 71 known genes. Candidate genes have not been proposed for Bmd5b at this time.

Bmd5c (bone mineral density 5c) is flanked by rs3710340 (173.868 Mb) and D1Kls6-1 within D1Mit149. This locus appears to be male specific. C3H/HeJ-derivedalleles at Bmd5c confer increased femoral trabecular thickness in males. Bmd5c may act dominantly on Bmd5b to prevent an increase in trabecular number. Thirty-one known genes are contained in the Bmd5c interval but no potential candidates have been proposedat this time.

References

• Original: J:139423 Beamer WG, et al., Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. J Bone Miner Res. 2007 Aug;22(8):1187-96
• All: 1 reference(s)