Poats1^C57BL/6JCrl
QTL Variant Detail

Summary

• QTL variant: Poats1^C57BL/6JCrl
• Name: post-ovarectomy adrenal tumor susceptibility 1; C57BL/6JCrl
• MGI ID: MGI:3775523
• QTL: Poats1 Location: Chr8:17082626-28849467 bp Genetic Position: Chr8, Syntenic

Variant origin

• Strain of Specimen: C57BL/6JCrl

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers susceptibility to adrenal gland tumorigenesis in females after prepubertal ovarectomy compared to DBA/2JCrl. (J:131752)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Poats1 interacts epistatically with Poats2 on chromosome 18.

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

J:131752

Genetic loci associated with susceptibility to post-gonadectomy adrenal tumorigenesis were mapped in 208 (C57BL/6J x DBA/2J)F2 female animals. A separate population of 125 (C57BL/6J x DBA/2J)F1 x C57BL/6J backcross females was also analyzed. Linkage analysis was performed with 192 microsatellite markers at an average resolution of 7.7 cM. Experimental animals were ovarectomized at 21- to 24-days of age and evaluated for weight gain monthly over 6 months and then sacrificed and assessed for arenal tumor status. Females from parental strain DBA/2J are susceptible to obesity and adrenocortical tumor development following prepubertal ovarectomy, which is similar to Cushing's syndrome in postmenopausal women. Ovarectomized C57BL/6J females do not develop adrenocortical tumors or obesity.

Significant linkage to post-ovarectomy weight gain mapped to mouse Chromosome 7 with LOD=4.79 in the F2 population. The QTL is located between SNP markers rs13479333 (37 cM; 80.35 Mb) and rs4226783 (50 cM; 100.08 Mb). This locus isnamed Powg (post-ovarectomy weight gain).

Suggestive linkage to post-ovarectomy weight gain in F2 animals was detected on chromosomes 11 (LOD=2.84), 1 (LOD=2.65), 5 (LOD=2.2), 14 (LOD=2.17), and 3 (LOD=2.14).

Significant linkage to post-ovarectomy susceptibility toadrenal gland tumors mapped to mouse Chromosome 8 (LOD=5.57) in the F2 population. The QTL is located between SNP markers rs32607714 (8 cM; 17.03 Mb) and rs6382288 (11 cM; 29.47 Mb). This locus is named Poats1 (post-ovarectomy adrenal tumor susceptibility 1). Homozygosity for C57BL/6J-derived alleles at Poats1 appears to be associated with susceptibility to adrenocortical tumorigenesis in ovarectomized female animals. The Poats1 QTL region contains 123 genes. Sfrp1 was identified as a potential candidate gene based on positive expression in the adrenal gland, and gene expression appears to be down-regulated in tumorigenic adrenal gland tissue. However, sequence analysis of Sfrp1 did not detect polymorphisms in the coding region or promoter sequences of parental strains. Suggestive linkage to adrenal gland tumors was detected on mouse Chromosome 10 (LOD=2.2).

Pair-wise analysis detected significant interaction for Poats1 and a locus on chromosome 18 between 80 Mb (52 cM) and 90 Mb (58cM) with LOD=8.32. This locus is named Poats2 (post-ovarectomy adrenal tumor susceptibility 2). The region contains 62 genes but no candidates for Poats2 have yet been identified.

References

• Original: J:131752 Bernichtein S, et al., Adrenal gland tumorigenesis after gonadectomy in mice is a complex genetic trait driven by epistatic loci. Endocrinology. 2008 Feb;149(2):651-61
• All: 1 reference(s)