Experiment
Genome scan using 141 microsatellite markers at an average spacing of 15 cM was performed on a (BALB/c x C57BL/6)F2 intercross population and on C57BL/6 x (BALB/c x C57BL/6)F1 and BALB/c x (BALB/c x C57BL/6)F1 backcross populations to identify QTLs associated with the regulation of clonogenic keratinocyte stem cell colony size. Parental strain C57BL/6 exhibits larger populations of large colonies compared to BALB/c, while BALB/c exhibits larger populations of small colonies compared to C57BL/6.
Significant linkages were detected on mouse Chromosomes 9 and 4 and were designated Ksc1 (keratinocyte stem cell locus 1) and Ksc2 (keratinocyte stem cell locus 2), respectively.
Ksc1 maps from 35 cM - 49 cM between D9Mit104 and D9Mit273 on mouse Chromosome 9 with peak linkage at D9Mit262 (41 cM, LOD=3.88). C57BL/6-derived alleles confer increased numbers of small keratinocyte stem cell colonies at Ksc1. Interestingly, Psl1, a QTL linked to skin tumor promotion, overlaps with Ksc1. Candidate genes mapping to theregion of Ksc1 include Map2k1, Rora, Anxa2, Adam10, Foxb1, Bmp5, Onecut1, Tcf12, Omt2a, and Omt2b.
Ksc2 maps from 1.9 cM - 6.5 cM between D4Mit264 and D4Mit2 on mouse Chromosome 4 with peak linkage at D4Mit264 (1.9 cM, LOD=3.05). BALB/c-derived alleles confer increased numbers of large keratinocyte stem cell colonies at Ksc2. Candidate genes mapping to the region of Ksc2 are Lyn, Mos, and Gem.
Suggestive QTLs associated with increased numbers of small colonies mapped to mouse 34.8 cM on Chromosome 1 (LOD=1.65 at D1Mit178) and to 35.5 cM on mouse Chromosome 6 (LOD=2.25 at D6Mit99).