Stheal9^MRL/MpJ
QTL Variant Detail

Summary

• QTL variant: Stheal9^MRL/MpJ
• Name: soft tissue heal 9; MRL/MpJ
• MGI ID: MGI:2176985
• QTL: Stheal9 Location: Chr9:76024387-76024534 bp Genetic Position: Chr9, Syntenic

Variant origin

• Strain of Specimen: MRL/MpJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased wound healing compared to SJL/J. (J:73197, J:127710)
• Inheritance: Other (see notes)

Notes

Stheal9 exhibits additive inheritance.

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

J:73197

Genome scan at a resolution of 15 cM was performed on 633 (MRL/MpJ x SJL/J)F2 animals to identify QTLs associated with wound healing at different time intervals. Parental strain MRL/MpJ exhibits complete healing of ear hole wounds whereas SJL/J animals heal approximately 25% of the wound. Significant QTLS affecting soft tissue healing, Stheal1-9, were mapped to 6 different mouse chromosomes. Stheal1 maps to 49.2 cM on mouse Chromosome 1 spanning 36.9 cM - 81.6 cM with a maximum LOD score of 7.06 at D1Mit334. MRL/MpJ-derived alleles confer increased wound healing in a dominant fashion at Stheal1. Stheal2 maps to 63.1 cM on mouse Chromosome 3 spanning 49.7 cM - 78.5 cM with a maximum LOD score of 6.18 at D3Mit217. MRL/MpJ-derived alleles confer increased wound healing in a dominant fashion at Stheal2. Stheal3 and Stheal4 map to 17.9 cM and 51.3 cM on mouse Chromosome 4, respectively. The peak LOD score of Stheal3 is centered at D4Mit214 (LOD=7.26) and the peak LOD score of Stheal4 is centered at D4Mit31 (LOD=6.82). MRL/MpJ-derived alleles confer additively-inherited increase in wound healing at Stheal3 and Stheal4. Stheal5 maps to 37 cM on mouse Chromosome 6 with a peak LOD score of 4.5 at D6Mit261. MRL/MpJ-derived alleles confer additively-inherited increase in wound healing at Stheal5. Stheal6 and Stheal7 map to 52.4 cM and 66 cM on mouse Chromosome 7 with peak LOD scores of 4.84 and 4.26 at D7Mit220 and D7Mit12, respectively. SJL/J-derived alleles confer increased wound healing in a dominant fashion atStheal6 while MRL/MpJ-derived alleles confer additively-inherited increase in wound healing at Stheal7. Stheal8 and Stheal9 map to 33 cM and 43 cM on mouse Chromosome 9 with peak LOD scores of 14.18 and 16.11 at D9Mit207 and D9Mit270, respectively. MRL/MpJ-derived alleles confer additvely-inherited increase in wound healing at Stheal8 and Stheal9. A suggestive QTL, Stheal10, mapped to 65 cM on mouse Chromosome 13 with LOD=3.03 at D13Mit228. Authors note that Stheal6 and Stheal10 maybe identical to wound healing QTLs Heal6 and Heal8, respectively, identified by McBrearty et al. LOD scores at all QTLs did not vary significantly with respect to time interval.

J:127710

The effects of tissue regeneration QTLs Stheal8 (33 cM) and Stheal9 (43 cM) on mouse Chromosome 9 were further analyzed using congenic animals. A congenic line was constructed which carries MRL/MpJ-derived DNA from D9Mit207 (33 cM) to D9Mit151 (72 cM) onan SJL/J genetic background. This donor segment contains both Stheal8 and Stheal9. Donor strain MRL/MpJ displays significantly better wound healing compared to background strain SJL/J.

SJL.MRL-(D9Mit207-D9Mit151) male congenic displayed increased healing with 12% smaller ear wound holes at 15- and 25-days after ear punch compared to SJL/J control males. This trend was also seen in female congenic animals although not at a statistically significant level.

Fine map analysis of the chromosome 9 region containing Stheal8 and Stheal9 was performed using an extended set of 1,564 male and female (MRL/MpJ x SJL/J)F2 animals and 23 polymorphic markers spaced approximately 4.2 Mb apart.

Four separate peaks were detecting suggesting Stheal8 and Stheal9 may be comprised of multiple linked loci.

The Stheal8 peak mapped between 61 Mb - 64 Mb with LOD=4.3 in males and LOD=5.3 in females. A separate peak distal to Stheal8 was detected at 69 cM - 85 Mb. Adam10 and Ttk are potential candidate genes for this locus.

Stheal9 was the third peak at 85 Mb (D9Mit196) - 90 Mb (D9Mit9) with LOD=8.8 in males and LOD=7.7 in females. Stheal9 displayed the strongest effect explaining 36% of the phenotypic variance. Tbx18 is a potential candidate gene for Stheal9.

The fourth peak mapped distal to Stheal9 at 94 Mb - 97.5 Mb.

Bayesian shrinkage analysis reduced the Stheal8 interval to 1.7 Mb between 60.8 Mb and 62.5 Mb. Stheal9 was reduced to a 1.3 Mb interval between 86.3 Mb and 87.6 Mb, and peak 4 was reduced to a 1.3 Mb interval between 94.2 Mb and 95.5 Mb.

References

• Original: J:73197 Masinde GL, et al., Identification of Wound Healing/Regeneration Quantitative Trait Loci (QTL) at Multiple Time Points that Explain Seventy Percent of Variance in (MRL/MpJ and SJL/J) Mice F(2) Population. Genome Res. 2001 Dec;11(12):2027-33
• All: 2 reference(s)