Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

BACKGROUND: Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F(2) female mice: F(2)A(y) mice (F(2) mice with the A(y) allele) and F(2) non-A(y) mice (F(2) mice without the A(y) allele). These were produced by crossing B6 females and DDD.Cg-A(y) males. DDD.Cg-A(y) is a congenic mouse strain for the A(y) allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The A(y) allele is dominant and homozygous lethal; therefore, living A(y) mice are invariably heterozygotes. RESULTS: Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F(2) non-A(y) mice, and on chromosomes 2, 6, and 12 for F(2)A(y) mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. CONCLUSIONS: The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes responsible for the QTLs will be essential for understanding the molecular basis of X-zone function, which is currently unclear.