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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.

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