Ecgnq1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ecgnq1^C57BL/6J
• Name: eccrine gland number QTL 1; C57BL/6J
• MGI ID: MGI:5882688
• QTL: Ecgnq1 Location: Chr1:103278062-120535225 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

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

J:226062

Reciprocal changes in hair cover and eccrine gland density are required for efficient thermoregulation in humans. The molecular mechanisms that specifically lead to the formation of eccrine glands as opposed to hair follicles and the mechanisms that govern eccrine gland patterning are poorly understood.

The mouse, a rare exception among mammals, has both hair and eccrine glands interspersed in a distinct domain of the hindfoot where the density of the two ectodermal appendage types can be easily scored. The skin between the footpads exhibits both eccrine glands and hair follicles interspersed as they are found in human hairy skin; the relative numbers of each are fixed within an inbred strain but are highly variable between strains. C57BL/6 mice have far more hair follicles than FVB/N mice; in contrast, the FVB/N mice have four times more eccrine glands in the same region than C57BL/6. There is also a subtle but significant increase in the number of eccrine glands in the footpads of FVB/N mice relative to C57BL/6 mice.

To examine the underlying genetic differences in eccrine gland and hair follicle number in the two strains, 647 animals were generated from an (FVB/N x C57BL/J)F2 cross for analysis. The numbers of eccrine gland and hair follicles were scored by averaging the number of each appendage type across the left and right hind feet in epidermal preparations. Ninety individuals were selected from the highest and lowest eccrine gland and hair follicle numbers. Tail genomic DNA was purified and whole genome SNP genotyping was carried on the Illumina MD mouse panel that carried 833 informative SNPS to distinguish between C57BL/6 and FVB/N strains. QTL mapping analysis was performed using the J/qtl 1.3.3 software. Data was permuted 1,000 times to assess significance.

Two overlapping QTL were identified on Chromosome 1, fine mapping of the region using 483 F2 animals further refined the critical intervals:

QTL Ecgnq1 (eccrine gland number QTL 1) mapped between 103.35 (rs30596698) - (rs3678634) 120.6 Mb on Chr 1 with a LOD score of 27.9, p<0.050, accounting for 76% of trait variance. [Fig 2.A,C]

QTL Hfnq1 (hair follicle number QTL 1) mapped to 1.5 LOD support interval between 93.38 (rs6268443) - (rs33345376) 123.7 Mb on Chr 1 with a LOD score of 18.6, p<0.05, accounting for 61% of trait variance. [Fig2 B, D]

QTL Hfnq2 (hair follicle number QTL 2) was identified on Chr 7 with a LOD score of 5.06.

The relative expression of genes from the Chr 1 QTLs in the developing plantar skin of C57BL/6J and FVB/N mice at P2.5, a stage when the early primordia of ectodermal appendages are morphologically evident in the interfootpad regions, were evaluated. Of the genes evaluated only En1 and Serpinb13 showed preferential expression in FVB/N, whereas Tmem177 showed preferential expression in C57BL/6.

The FVB/N allele of En1 was expressed at a higher level than the C57BL/6J allele in the skin taken from the ventral surface of the feet of F1 animals at the time that placodes were forming. Reduced En1 expression lead not only to decreased eccrine gland number but also to increased hair follicle number in the interfootpad. Modulation of En1 levels was identified as a driver of natural differences in eccrine gland and hair follicle density between FVB/N and C57BL/6 inbred mouse strains. Differences in the activity of cis-regulatory regions of the En1 gene appear to play a significant role in dictating the preponderence of hair follicles and paucity of eccrine glands in the C57BL/6J background, and to drive the inverse trait distribution in the FVB/N background.

References

• Original: J:226062 Kamberov YG, et al., A genetic basis of variation in eccrine sweat gland and hair follicle density. Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):9932-7
• All: 1 reference(s)