Igf1sl4^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Igf1sl4^C57BL/6J
• Name: IGF-1 serum levels 4; C57BL/6J
• MGI ID: MGI:3046887
• QTL: Igf1sl4 Location: unknown Genetic Position: Chr11, cM position of peak correlated region/allele: 4.7 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers decreased serum IGF-1 levels and decreased BMD in conjunction with C3H/HeJ-derived alleles at Igf1sl1. (J:66640)

Notes

Igf1sl1 and Igf1sl4 exhibit epistatic interaction. Homozygosity for C3H/HeJ-derived alleles at Igf1sl4 negates the IGF-1 lowering effect of Igf1sl1. When Igf1sl4 is homozygous or heterozygous for C57BL/6J-derived alleles the effect of Igfsl1 can be observed.

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

J:66640

Phenotypically extreme female animals from a (C57BL/6J x C3H/HeJ)F2 intercross were genotyped at 114 polymorphic loci at a resolution of 14 cM to identify QTLs associated with serum IGF-1 levels and bone mineral density (BMD). Parental strain C3H/HeJ exhibits increased serum IGF-1 and increased BMD compared to C57BL/6J. Since osteoblasts from C3H/HeJ animals secrete more IGF-1 compared to osteoblasts from C57BL/6J animals a correlation between IGF-1 levels and BMD was investigated. 682 F2 female animals were used in the final analysis.

Significant linkage mapped to 51 cM on mouse Chromosome 6 near D6Mit150 (LOD=9). This locus in named Igf1sl1 (IGF-1 serum level 1). C3H/HeJ-derived alleles confer decreased serum IGF-1 at this locus. A correlation betweenserum IGF-1 levels and BMD was observed for Igf1sl1.

Igf1sl2 mapped to 51 cM on mouse Chromosome 10 near D10Mit95 (LOD=4.5). C3H/HeJ-derived alleles confer increased serum IGF-1 at this locus. Correlation between serum IGF-1 levels and BMD was not observed for Igf1sl2. The Igf1 (48 cM) gene maps very close to this locus, just 3 cM proximal to Igf1sl2.

Igf1sl3 mapped to 32 cM on mouse Chromosome 15 near D15Mit209 (LOD=4.4). C3H/HeJ-derived alleles confer increased serum IGF-1 at this locus. Correlationbetween serum IGF-1 levels and BMD was not observed for Igf1sl1.

A fourth QTL, Igf1sl4, was identified via pairwise interaction analysis. Ifg1sl4 maps to 1.1 cM on mouse Chromosome 11 near D11Mit71 and is epistatic to Igf1sl1 on mouse Chromosome 6. Homozygosity for C3H/HeJ-derived alleles at Igf1sl4 negates the IGF-1 lowering effect of Igf1sl1. When Igf1sl4 is homozygous or heterozygous for C57BL/6J-derived alleles the effect of Igfsl1 can be observed. Correlation between serum IGF-1 levels and BMD wasobserved for Igf1sl4. Potential candidate genes mapping near Igf1sl4 are Igfbp1 (1.3 cM) and Igfbp3 (1.35 cM).

To test the theory that C3H/HeJ-derived alleles at Igfsl1 and C57BL/6J-derived alleles at Igfsl4 impact serum IGF-1 and BMD, a congenic line (B6.C3H-6) carrying C3H/HeJ-derived DNA on chromosome 6 on the genetic background of C57BL/76J was studied. Congenic animals exhibit a 16% decrease in serum IGF-1 and a 4% decrease in femoral BMD compared to C57BL/6J.

References

• Original: J:66640 Rosen CJ, et al., Mapping quantitative trait loci for serum insulin-like growth factor-1 levels in mice. Bone. 2000 Oct;27(4):521-8
• All: 1 reference(s)