Pain2^C3H/HeN
QTL Variant Detail

Summary

• QTL variant: Pain2^C3H/HeN
• Name: pain 2; C3H/HeN
• MGI ID: MGI:3582724
• QTL: Pain2 Location: Chr15:68645339-68645626 bp Genetic Position: Chr15, Syntenic

Variant origin

• Strain of Specimen: C3H/HeN

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers high pain compared to C58/J. (J:99476)
• Inheritance: Dominant

Notes

This QTL is influenced by the caging effect. Pain2 shows high significance in individually-caged female animals. Homozygosity for C3H/HeN-derived alleles at Pain2 confers high autonomy in females with reduced penetrance (40%). However, heterozygosity for C58/J- and C3H/HeN-derived alleles at Pain2 is highly penetrant (97%) for low autonomy in females.

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

J:99476

Linkage analysis was used in a backcross population of 267 (C3H/HeN x C58/J)F1 x C3H/HeN mice to confirm QTL using autotomy behavior in a neuroma model of neuropathic pain.

C3H/HeN mice consistently show high levels of autotomy behavior while C58/J mice consistently show low levels. Nine polymorphic markers spaced at 3-12 cM intervals on mouse Chromosome 15 were used in the analysis.

10.21.2015 Curator Note: Because Pain1 was originally mapped in J:70963 in 2001 using (AXB) and (BXA) RI strains, which differ from the cross used here, we consider the current mapping study to be a separte mapping experiment and have named the QTL Pain2.

Peak linkage to the pain phenotype, Pain2, was detected at marker D15Mit68 (44.1 cM) with LOD=3.0. The 1-LOD support interval of Pain2 spans 40 cM - 48 cM, and this locus explains 5.2% of the phenotypic variance.

The LOD plot shows a second peak at approximately 25 cM suggesting that another QTL affecting the pain phenotype may be present in addition to Pain2.

C3H/HeN-derived alleles at Pain2 confer a dominantly inherited high pain phenotype.

J:124159

Linkage analysis was performed on 370 (C3H/HeN x C58/J)F1 x C3H/HeN backcross animals to identify genetic loci involved with neuropathic pain. Animals were surgically denervated at the hindpaw at 2-3 months of age and evaluated weekly for autotomy.

One-third of the animals were group-housed and two-thirds of the animals were individually-housed. Parental strain C3H/HeN typically displays high pain (autotomy) phenotype and parental strain C58/J typically displays low pain phenotype. Investigators observed group housing affects pain response phenotype. A panel of 100 polymorphic markers spaced 15 cM - 20 cM apart was used for genome scan.

A locus on mouse Chromosome 15, the previously identified Pain1 QTL at 44 cM, was detected only in the individually-housed backcross mouse population with a higher level of significance in females. Peak linkage to autotomy in females mapped to 32 cM at marker D15Mit277 with LOD=3.3. Pain1 explains 17.1% of the variance in females and 3.4% of the variance in males.

10.29.2015 Curator Note: Because Pain1 was originally mapped in J:70963 in 2001 using (AXB) and (BXA) RI strains, which differ from the mouse population used here, we consider the current study a separate mapping experiment and have equated this QTL with Pain2. Pain2 was originally mapped in J:99476 in 2005 using the same backcross population used here.

Homozygosity for C3H/HeN derived alleles at Pain2 confers high autotomy in females with reduced penetrance (40%). However, heterozygosity for C58/J and C3H/HeN derived alleles at Pain2 confers low autotomy in female animals with high penetrance (97%).

References

• Original: J:99476 Devor M, et al., pain1: A neuropathic pain QTL on mouse chromosome 15 in a C3HxC58 backcross. Pain. 2005 Aug;116(3):289-93
• All: 3 reference(s)