Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  7
• Reference
  J:216324 Okumura K, et al., Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas. PLoS One. 2014;9(5):e97201
• ID
  MGI:5795987

Genes

Gene	Assay Type
Stmm1	susceptibility/resistance
D7Mit21
D7Mit98
D7Mit323
D7Mit130

Notes

• Experiment
  The authors previously reported the mapping of QTL, Stmm1 and Stmm2 (skin tumor modifier of MSM), which confer resistance to skin tumor development on mouse chromosome 7 in a cross between the resistant Japanese wild-derived inbred strain MSM/Ms and the susceptible strain FVB/NJcl. [J:193231, PMID:22843548].
  
  Stmm1 mapped near markers D7SNP507 and D7SNP513. Stmm2 mapped near markers D7SNP6 and D7Mit10. In the present study resistant F1 backcross mice were selected for backcrossing to FVB/NJcl mice to generate two N10 congenic lines that spanned either the Stmm1 (congenic line a) or the Stmm2 (congenic line b) locus to confirm the presence of low-penetrance susceptibility genes in these regions. [Fig 1A.]
  
  Each congenic line was then subject to the DMBA-TPA skin carcinogenesis experiment. FVB/MSM heterozygous mice of line a, developed significantly fewer papillomas than FVB/N homozygous mice; while FVB/MSM heterzygous mice of congenic line b developed about the same number of papillomas as control FVB/N mice. The results suggest that Stmm1 has a stong suppressive effect on papilloma development.
  
  A series of congenic lines (c-i, Table 1.) containing different overlapping regions were generated from mice of line (a) FVB.MSM-(D7Mit21-D7Mit98) . These subcongenics were subjected to the DMBA/TPA chemical carcinogenesis protocol and their papilloma development was monitored for a period of 20 weeks. Of the seven subcongenic lines tested, four lines (c,d,e,and f) showed significant linkage with papilloma incidence. By determining the minimum overlapping regions within the four lines and excluding the regions of the lines that did not show an effect (g,h,and i) the location of the Stmm1 region was narrowed down to an interval between D7Mit323 at 54.45 cM and D7Mit130 at 57.52 cM. This region did not overlap with the previously reported Skts1 locus. [Fig 2A.]
  
  Detailed investigation of allelic imbalance analysis was performed using 12 informative microsatillite markers. Two imbalance peaks were detected within the minimum overlapping region of 3 cM identified with the multiple congenic lines of Stmm1; one localized between D7Mit96 (100.5 Mb) and D7Mit131 (103.87 Mb) and the other between D7Mit95 (105.75 Mb) and D7Mit124 (107.68 Mb). When these two regions were combined the total physical size of the candidate region was cut down to about 5.4 Mb. Further congenic and somatic mapping will refine the candidate region to facilitate gene identification.
  
  To gain insight into the function of the Stmm1 locus, analysis with BrdU-LRC was carried out with congenic lines. [Fig 4.]. The results suggest that gene(s) located within the Stmm1 locus may have an influence on the papillomagenesis step in the two stage skin carcinogenesis by regulating epidermal quiescent stem cells.