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QTL Variant Detail
QTL variant: DrsiC57BL/6NCrl
Name: DCC-related Spp1 induction; C57BL/6NCrl
MGI ID: MGI:3579882
QTL: Drsi  Location: Chr7:16637293-49159331 bp  Genetic Position: Chr7, Syntenic
Strain of Specimen:  C57BL/6NCrl
Allele Type:    QTL

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


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).

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)

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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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