Drsi^C3H/HeNCrl
QTL Variant Detail

Summary

• QTL variant: Drsi^C3H/HeNCrl
• Name: DCC-related Spp1 induction; C3H/HeNCrl
• MGI ID: MGI:3579883
• QTL: Drsi Location: Chr7:16637293-49159331 bp Genetic Position: Chr7, Syntenic

Variant origin

• Strain of Specimen: C3H/HeNCrl

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers susceptibility to dystrophic cardiac calcification and injury-related Spp1 induction compared to C57BL/6NCrlBr. (J:89623)

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:89623

The Spp1 gene on mouse Chromosome 5 shows strong expression at sites of cardiac calcification induced by freeze-thaw injury. Inbred strain C3H/HeNCrlBr is susceptible to dystrophic cardiac calcinosis (DCC) and exhibits 20-fold increased Ssp1 mRNA induction after freeze-thaw injury compared to DCC-resistant strain C57BL/6NCrlBr. A previously identified locus on mouse Chromosome 7 named Dyscalc1 (21 cM) shows linkage to the DCC phenotype.

In this study, a congenic line named B6.C3-(D7Mit56-D7Mit230) was used to assess the effect of the Dyscalc1 locus on Ssp1 expression. The congenic carries C3H/HeNCrlBr-derived DNA between D7Mit56 (2.5 cM) and D7Mit230 (24.5 cM), which contains the Dyscalc1 locus, on a C57BL/6NCrlBr genetic background. Similar to the DCC-susceptible donor strain C3H/HeNCrlBr, the congenic exhibits DCC susceptibility and significantly increased Spp1 induction following cardiac injury. Since the congenic Spp1 locus is derived from background strain C57BL/6NCrlBr, this finding shows that DCC susceptibility is not controlled by Spp1. However, the locus between D7Mit56 and D7Mit230 appears to be a trans-activator of Spp1 expression and controls DCC susceptibility.

A potential candidate gene found within the congenic interval is Tgfb1 (6.5 cM). Tgfb2 has been shown to induced Opn1 and shows greater induction in the necrotic tissues of C3H/He animals compared to C57BL/6 animals. Since Tgfb1 (6.5 cM) and Dyscalc1 (21 cM) map to different positions it is not clear if they represent the same underlying cause for cardiac injury related Opn1 induction. For this reason the locus between D7Mit56 and D7Mit230 is named Drsi (DCC-related Spp1 induction).

References

• Original: J:89623 Aherrahrou Z, et al., A locus on chromosome 7 determines dramatic up-regulation of osteopontin in dystrophic cardiac calcification in mice. Am J Pathol. 2004 Apr;164(4):1379-87
• All: 1 reference(s)