Coro2a, An Expression Quantitative Trait Gene UnderlyingEstq1, Controls Uterine Responsiveness to Estradiol

A bstract The response of the uterus to 17β-estradiol (E 2 ) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous studies from our laboratory using high (C57BL6/J; B6) and low uterine responders (C3H/HeJ; C3H) to E 2 led to the identification of Estq1-Estq5 , five quantitative trait loci (QTL) controlling phenotypic variation in uterine growth and eosinophilic leukocyte infiltration. Transcriptional profiling subsequently identified coronin actin binding protein 2A ( Coro2a ) as a candidate for an expression quantitative trait gene (eQTG) underlying Estq1 . Here we show that like mRNA expression, allele specific expression of CORO2A in both the uterine epithelium and stroma similarly co-segregates with uterine responsiveness. Utilizing B6.C3H congenic mice carrying the Coro2a C3H allele, we confirm the genetic linkage between Coro2a and Estq1 . Lastly, we show that B6- Coro2a -/- and B6- Coro2a B6/- mice phenocopy uterine responsiveness of mice carrying the Coro2a C3H/C3H and Coro2a B6/C3H alleles respectively, consistent with a haploinsufficiency model of genetic control. Together, these results identify Coro2a as the eQTG underlying Estq1 , and establish a critical role for Coro2a in E 2 -regulated responses.