Phenotypic impact on coat color and uterine development in mice carrying a missense mutation associated with bovine White Heifer Disease.

White Heifer Disease (WHD) is a congenital reproductive abnormality, especially in white female offspring in certain breeds of cattle like Belgian Blue. The roan locus was reported to affect coat color and fertility. It was suggested that a missense mutation (Ala218Asp) in the transmembrane domain of Kit ligand (KITL) gene was responsible for WHD. Here we generated two types of knock-in (KI) mice to reproduce the missense KITL mutation using pigmented agouti ICR mice. KI mice carrying compound mutations mimicking bovine transmembrane domain showed moderate coat color change, but single missense mutation KI did not. None of them exhibited uterine abnormalities, suggesting that localized gene modification may not fully affect murine KITL function.