Svtms^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Svtms^C57BL/6J
• Name: survival time modifier of Sod2; C57BL/6J
• MGI ID: MGI:3626354
• QTL: Svtms Location: Chr13:107613580-119476372 bp Genetic Position: Chr13, cM position of peak correlated region/allele: 59.18 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased survival in the presence of Sod2^tm1Cje compared to DBA/2J. (J:108213)
• Inheritance: Recessive

Notes

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

J:108213

The mitochondrial superoxide dismutase mutation Sod2^tm1Cje results in lethality, but phenotype and survival time is modified by genetic background. C57BL/6J animals with Sod2^tm1Cje develop dilated cardiomyopathy and die at 15 days gestation, whereas DBA/2J animals with Sod2^tm1Cje develop metabolic acidosis and die at approximately 8 days after birth.

Genome scan performed on animals from a C57BL/6-Sod2^tm1Cje x (C57BL/6 x DBA/2-Sod2^tm1Cje)F1 backcross detected preliminary linkage to survival time on mouse Chromosomes 9, 13, and 17. 217 microsatellite markers at an average spacing of 6.8 cM were used for the genome scan. Recombinant congenic Sod2^tm1Cje strains derived from C57BL/6 and DBA/2J were constructed to map putative survival time QTLs.

Significant linkage to increased survival time in the presence of Sod2^tm1Cje mapped to distal mouse Chromosome 13 between D13Mit288 and D13Mit35. This locus was further narrowed to a 10 Mb region around D13Mit35 (17 cM; 116.1 Mb) andis named Svtms (survival time modifier of Sod2). The presence of a DBA/2J-derived allele at Svtms confers increased lifespan of Sod2^tm1Cje recombinant congenic animals to a degree similar to DBA/2J-Sod2^tm1Cje animals. Potential candidate genes mapping to this region are Nln, Ndufs4, Mrps30, and Nnt (64 cM). Few SNPs have have been identified between C57BL/6J and DBA/2J for Nln, Ndufs4, and Mrps30.

C57BL/6J was found to have shorter Nnt cDNA lacking exons 7 - 11 compared to DBA/2J, due to a 17.8 kb deletion. Western blot analysis revealed an absence of Nnt protein in C57BL/6 tissues, whereas Nnt protein was present in tissues from DBA/2J, FVB/NJ, and C3H/HeJ. The null mutation is present only in C57BL/6J animals from The Jackson Laboratory, and is not found in otherclosely related C57BL/6 strains. The evidence supports Nnt as a candidate gene for Svtms.

References

• Original: J:108213 Huang TT, et al., Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase. Hum Mol Genet. 2006 Apr 1;15(7):1187-94
• All: 1 reference(s)