Pbd1^SAMP2
QTL Variant Detail

Summary

• QTL variant: Pbd1^SAMP2
• Name: peak bone density 1; SAMP2
• MGI ID: MGI:3027144
• QTL: Pbd1 Location: Chr11:102344123-112384123 bp Genetic Position: Chr11, cM position of peak correlated region/allele: 54.34 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: SAMP2

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased bone density compared to SAMP6. (J:52867)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:52867

90 polymorphic loci were screened in animals from a (SAMP2/Jcl x SAMP6/Jcl)F2 intercross using a selective genotyping strategy to identify QTLs involved in peak bone mass. SAM (Senescence Accelerated Mouse) inbred strain SAMP6 exhibits lower peak bone mass compared to the SAMP2 inbred strain. Significant loci were detected on mouse Chromosome 13 (Pbd2, LOD = 5.8 at 8.3 cM) with a QTL interval spanning 9 cM - 10 cM, and mouse Chromosome 11 (Pbd1, LOD = 10.8 at 51.8 cM) with a QTL interval spanning 42 cM -58.51 cM. Possible candidate genes for Pbd1 are Col1a1 (Cola1) and Csf3 (Csfg). Suggestive loci were also detected on mouse Chromosome 9 and mouse Chromosome X at 49 cM in linkage with DXMit97.

J:122920

Peak bone density QTL Pbd1 (51.8 cM) on mouse Chromosome 11 was refined using congenic line analysis. A 39 cM interval of SAMP2-derived DNA from D11Mit242 (31 cM) to D11Mit167 (71 cM) encompassing the Pbd1 locus was introgressed onto a SAMP6 genetic background. This congenic line is named P6.P2-Pbd1. Males age 16 weeks from donor strain SAMP2 display significantly increased cortical thickness index (CTI) compared to males from background strain SAMP6, and P6.P2-Pbd1 congenic males display higher CTI thanSAMP6 males thus confirming the effect of Pbd1. The QTL has a similar effect in 16 week old females.

A series of subcongenic lines derived from P6.P2-Pbd1 narrowed the Pbd1 interval to a 10.1 Mb region between D11Mit52 (62 cM) and D11Mit184 (78 cM). Subsequent SNP analysis refined the interval to 10 Mb between Itga2b (68 cM) and D11Mit184 (78 cM). The refined Pbd1 locus also shows significant linkage to midshaft bone area fraction, short axis length, and oblateness, with SAMP2-derived alleles increasingthese values compared to SAMP6.

Gene expression analysis was performed on 114 genes found between Itga2b and D11Mit184 using bone and kidney mRNA from SAMP6 and subcongenic line SS7. In bone mRNA, Plcd3 (63 cM) displayed 2-fold increased expression in SS7 relative to SAMP6, while Arsg displayed 2-fold reduced expression. In kidney mRNA, Axin2 (70 cM), Rgs9 (70 cM), and sequence Q8CE14_MOUSE displays ~2-fold reduced expression in SS7 relative to SAMP6. Of particular interest, Cacng4 displays 9-fold decreased expression in SS7 kidney mRNA relative to SAMP6.

The Pbd1 locus is syntenic to human chromosome 17q21.31 and 17q23.2-q24.3. These regions have also been associated with bone characteristics in humans.

References

• Original: J:52867 Shimizu M, et al., Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain. Mamm Genome. 1999 Feb;10(2):81-7
• All: 2 reference(s)