Heal4^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Heal4^C57BL/6J
• Name: wound healing/regeneration 4; C57BL/6J
• MGI ID: MGI:2669644
• QTL: Heal4 Location: Chr15:94527592-94527707 bp Genetic Position: Chr15, cM position of peak correlated region/allele: 48.65 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Other (see notes)

Notes

Heal4 exhibits additive inheritance.

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

J:50111

MRL/MpJ-Fas^lpr is the only inbred mouse strain capable of complete wound healing after introduction of surgical holes to the ear. Healing includes angiogenesis, regeneration of hair follicles, sebaceous glands, cartilage, and a complete lack of scarring. MRL/MpJ animals exhibit the same super healing trait as MRL/MpJ-Fas^lpr. C57BL/6NTac exhibits poor healing and when crossed to MRL/MpJ-Fas^lpr F1 animals display intermediate healing phenotype with wide variability.

(MRL/MpJ-Fas^lpr x C57BL/6NTac)F2 animals and (MRL/MpJ-Fas^lpr x C57BL/6NTac)F1) x MRL/MpJ-Fas^lpr backcross animals were used to map QTLs involved in wound healing. A genome scan was performed on the 19 autosomes with an average marker density of 20 cM. Polymorphisms could not be detected on the X chromosome and therefore was excluded from the scan. Ninty-two markers detected alleleic variants in the parental strains and were used for genotyping the segregating populations. Markers were chosen with 20cM between to generate a complete genome-wide scan.

The 92 polymorphic microsatellite markers were used to map the wound healing/regeneration trait in 101 mice from the (MRL/MpJ-Fas^lpr x C57BL/6NTac)F2 intercross. Threshold values for significance were determined by permutaion testing, based on a regression model (p ^0.05).

Values for an additive model of inheritance in the F2 were calculated in terms of a likelihood ratio statistic (LRS). The threshold for suggestive significance was LRS 3.3; for significant linkage LRS > 10.7. Threshold values in the backcross were LRS>3.7 and 11.8 respectively.

TABLE 2:

Heal2 and Heal3 mapped to Chromosome 13 at 11cM ( p=0.0019, LRS = 9.7 at D13Mit115) and 60cM ( p=0.0010, LRS = 10.8 at D13Mit129), respectively, in the (MRL/MpJ-Fas x C57BL/6NTac)F2 intercross and were confirmed in the (MRL/MpJ-Fas x C57BL/6NTac)F1) MRL/MpJ-Fas backcross.

Significant QTL Heal1 mapped to chromosome 8 at 49cM (p=0.0011, LRS = 10.7 at D8Mit211), and Heal4 mapped to chromosome 15 at 56.8cM (p=0.0011, LRS = 10.7 at D15Mit244) in the (MRL/MpJ-FasxC57BL/6NTac)F2 intercross.

Highly suggestive QTLs Heal7 and Heal8 also mapped to Chromosome 13 at 32cM (p=0.0014, LRS = 10.2 at D13Nds1) and 44 cM (p=0.0014, LRS = 10.2 at D13Mit191), respectively, in only the F2 intercross. Msx2 is found in the region near D13Nds1 and is expressed in regenerating amphibian tissue as well as regrowing fingertips in neonatal mice.

Heal6, also highly suggestive, mapped to Chromosome 7 at 52.4cM (p=0.0014, LRS = 10.2 at D7Mit220) in the (MRL/MpJ-Fas x C57BL/6NTac)F1) x MRL/MpJ-Fas backcross. Candidate genes for Heal1 include Gnao1 [Table 4].

Heal5 mapped to Chromosome 12 at 52cM ( p=0.0009, LRS = 10.9 at D12Mit132) also in only the backcross. The gene encoding retonic acid gamma (Rarg), is found near the Heal5 QTL. The retinoic acid pathway is known for its role in regeneration in amphibians.

All healing QTLs are additive and associated with MRL/MpJ-Fas alleles except Heal1 where the healing phenotype is associated with C57BL/6NTac alleles. Heal3 may be recessive; animals homozygous for MRL/MpJ-Fas alleles show increased healing.

In the present study none of the healing QTLs nor the highly suggestive regions identified displayed linkage to the Fas gene.

References

• Original: J:82708 Blankenhorn EP, et al., Sexually dimorphic genes regulate healing and regeneration in MRL mice. Mamm Genome. 2003 Apr;14(4):250-60
• All: 1 reference(s)