Bnszq2^C3H
QTL Variant Detail

Summary

• QTL variant: Bnszq2^C3H
• Name: bone size QTL 2; C3H
• MGI ID: MGI:3618848
• QTL: Bnszq2 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: C3H

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased bone size compared to C57BL/6J. (J:99483)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Bnszq2 was mapped using 917M mutant animals derived from a dominant ENU mutagenesis screen of C57BL/6J males.

Bnszq2 interacts with Bnszq1 on chromosome 4.

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

J:99483

Dominant ENU mutagenesis screening on the C57BL/6J background identified a male-specific reduced bone size mutant phenotype. At 16 weeks of age, males of the mutant line, designated 917M, exhibit 10%-13% reduction in total body bone area and 5%-8% reduced periosteal circumference of the tibia and femur midshaft compared to wild type C57BL/6J males. Male 917M animals also exhibit 17%-27% reduced cell proliferation and 23% increased apoptosis of periosteal osteoblasts compared to wild type C57BL/6J males. 917M females are not affected. Genetic loci involved in the mutant phenotype were mapped via a low resolution genome scan using 60 microsatellite markers (average spacing = 21 cM) and 129 (C57BL/6J-917M x C3H)F2 intercross animals.

Significant linkage to bone size mapped to 10.5 cM on mouse Chromosome 4 with LOD=7.9. This locus is named Bnszq1 (bone size QTL 1). When body weight was used as a covariate, the LOD scores for femur bone area, periosteal circumference, and endosteal circumference were 6.2, 9.1, and 5.6, respectively. Fine mapping using 8 additional chromosome 4 markers shifted peak linkage for periosteal circumference to 50 cM. It is unclear whether chromosome 4 harbors a single QTL or 2 separate QTL. This locus explains 38%-42% of the phenotypic variance. C57BL/6J-derived alleles at Bnszq1 confer decreased bone size in males. Potential candidate genes are Calb1 (10.5 cM), Igfbpl1, Casp8ap2 (11.4 cM), Gabrr1 (10.5 cM), Gabrr2 (10.5 cM), Cga (10.5 cM), Rragd (11.4 cM), Il11ra1 (12.7 cM), andMusk (26.3 cM).

A second locus named Bnszq2 (bone size QTL 2) mapped to 45 cM (LOD=4.9) on mouse Chromosome 1 and appears to interact with Bnsz1 on chromosome 4. C3H-derived alleles at Bnszq2 confer decreased bone size in males. The combined effect of Bnsz1 and Bnsz2 explains 60% of the phenotypic variance. Previously identified bone QTL mapping near Bnsz2 include Bmd1 (87.9 cM), Bmd5 (81.6 cM), and Pcir1 (84 cM).

A suggestive bone size locus mapped to 5 cM on mouse Chromosome 14 (LOD=4.7) when body weight was used as a covariate.

References

• Original: J:99483 Srivastava AK, et al., Identification of novel genetic loci for bone size and mechanosensitivity in an ENU mutant exhibiting decreased bone size. J Bone Miner Res. 2005 Jun;20(6):1041-50
• All: 1 reference(s)