Lsq1^A/J
QTL Variant Detail

Summary

• QTL variant: Lsq1^A/J
• Name: loss of tissue after ischemia QTL 1; A/J
• MGI ID: MGI:3795767
• QTL: Lsq1 Location: unknown Genetic Position: Chr7, Syntenic

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased tissue necrosis and decreased perfusion recovery after surgically-induced hindlimb ischemia compared to C57BL/6J. (J:135427)

Notes

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

J:135427

Linkage analysis was performed on 105 (C57BL/6J x BALB/cJ)F1 x BALB/cJ backcross progeny to identify QTL associated with tissue preservation and recovery following surgically-induced hindlimb ischemia. Parental strain C57BL/6J displays decreased tissue necrosis and increased perfusion recovery 21 days after surgical excision and ligation of the femoral artery compared to parental strain BALB/cJ. Genome scan was performed using 239 informative SNP markers spaced 6.8 cM apart.

Significant linkage mapped to 64 cM on mouse Chromosome 7 near rs13479513 (134.25 Mb) with LOD=7.96 for tissue necrosis and LOD=3.71 for perfusion ratio at day 21 after surgery. This locus is named Lsq1 (loss of tissue after ischemia QTL 1). The presence of a C57BL/6J-derived allele at Lsq1 confers protection from necrosis and increased perfusion ratio with a dominant mode of inheritance. Lsq1 also exhibits significant linkage with increased perfusion ratio at 7- and 14-days after surgery.

The existence of Lsq1 was confirmed using a consomic line carrying A/J-derived (susceptible) chromosome 7 on a C57BL/6J (resistant) genetic background. As expected, this consomic line, designated C57BL/6J-Chr7^A/J/NaJ, displays poor recovery and susceptibility to tissue necrosis after hindlimbischemia therefore validating a genetic locus on chromosome 7 affecting hindlimb ischemia phenotypes.

Lsq1 is not associated with wound healing as parental strains C57BL/6J and BALB/cJ do not display differences in rate of wound healing 1 week after dorsal skin hole punch.

SNP haplotype block analysis identified two ancestral haplotype blocks directly under the QTL peak that differ between C57BL/6J and BALB/cJ or A/J. The haplotype blocks span 1.7 Mb and 1.9 Mb and contain 21 and 16 known genes, respectively.

J:163182

Substitution of mouse Chromosome 7 of A/J into the C57BL/6 background transferred a portion of the characteristics of plantar and adductor perfusion and baseline collateral number of the A/J strain to the C57BL/6 strain. This confirms the mapping of mouse Chromosome 7 QTL Lsq1 as found by Dokun AO, Circulation 2008 Mar 4;117(9):1207-15 in J:135427.

References

• Original: J:135427 Dokun AO, et al., A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical hindlimb ischemia. Circulation. 2008 Mar 4;117(9):1207-15
• All: 1 reference(s)