Modvl5^C3H/HeSnJ
QTL Variant Detail

Summary

• QTL variant: Modvl5^C3H/HeSnJ
• Name: modifier of vacuolated lens 5; C3H/HeSnJ
• MGI ID: MGI:5775536
• QTL: Modvl5 Location: Chr18:68052156-68052311 bp Genetic Position: Chr18, Syntenic

Variant origin

• Strain of Specimen: C3H/HeSnJ

Variant description

• Allele Type: QTL

Notes

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

J:145456

Authors previously reported (J:131929) that the vl phenotypes are due to a mutation in an orphan G protein-couples receptor, Gpr161; and that penetrance of the vl NTD and cateract phenotypes are affected by genetic background, allowing three unlinked QTL to be mapped (Modvl1-3). In the current study additional QTL analysis was performed and two novel modifiers were mapped, Modvl4 and Modvl5.

To map the vl locus and to generate F2 vl/vl mice for QTL analysis, vl/vl C3H mice were crossed to three different inbred strains (C57BL/6J, CAST/EiJ and MOLF/EiJ. For the C57BL/6J and the CAST/EiJ crosses wild-type females were mated to C3H/HeSnJ-vl/vl males and for the MOLF/EiJ cross wild-type males were mated to C3H/HeSnJ-vlvl females to produce F1 progeny. F1 mice were then crossed to generate F2 progeny.

vl/vl mice were identified by the C3H/C3H geneotype of simple sequence length polymorphism markers flanking the vl locus. C57BL/6J:D1Mit143, D1Mit15; CAST and MOLF: D1Mit506, D1Mit15. For the B6 and CAST crosses, 86 and 94 F2 vl/vl mice were typed for genome scans and then analyzed for QTL. For the MOLF cross, 92 F2 vl/vl mice were typed for genome scan markers and analyzed for QTL.

For the (C57BL/6J x C3H/HeSnJ)F2 cross a QTL mapped to Chr 5 with a peak at 44 cM linked with marker D5Mit309, LOD=3.7. The B6 alleles segregated with the presence of a belly spot in a recessive fashion. Interestingly the same QTL was mapped previously when the adult spina bifida phenotype was used as a trait (Modvl1) but with the B6 allele segregating in a dominant fashion. These data suggest that the same locus influences both phenotypes.

Curator Note: Because a different phenotype was measured in this study we regard this QTL, mapping to the same location as Modvl1, as novel and have named it Modvl6, modifier of vacuolated lens 6.

When the belly spot phenotype was used as a trait in the (C3H/HeSnJ x MOLF/EiJ)F2 cross, two additional QTL were identified.

Modvl4, modifier of vacuolated lens 4, mapped to Chr 15 peaking at 15 cM linked to D15Mit252, LOD=4.4.

Modvl5, modifier of vacuolated lens 5, mapped to Chr 18 peaking at 41 cM linked with marker D18Mit50, LOD=5.0.

For both Modvl4 and Modvl5 the C3H allele segregates with the belly spot phenotype in an additive fashion while the MOLF alleles for these QTL are inherited with phenotypically normal F2 vl/vl progeny. Modvl4 and Modvl5 account for 12.7% and 16.8% of the F2 trait variance.

Phenotype based bioinformatics identified candidate genes for the modifiers [Table 6.] including two GPCRs that cause NTD or skin/pigmentation defects; Fzd6 for Modvl4 and Mc5r for Modvl5.

References

• Original: J:145456 Korstanje R, et al., Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics. 2008 Nov 12;35(3):296-304
• All: 3 reference(s)