A DNA insertional mutation results in microphthalmia in transgenic mice

Abstract

Transgenic mice were produced by microinjection of a human^Aγ-globin gene construct containing site 2 of the locus control region and the^Aγ-globin gene with its 3′ enhancer sequence. One transgenic mouse line 95′HS2γen91) displayed an altered phenotype when the insertion event of this transgenic line was homozygous. These animals lack the normal pigmentation seen in their hemizygous and non-transgenic littermates, thus appearing white with unpigmented eyes. In addition, their eyes are underdeveloped, consistent with the phenotype associated with mutations at themicrophthalmia (mi) locus. Backcrosses of transgenic mice withmi mutant mice result in phenotypes showing a lack of complementation, demonstrating that the site of transgene insertion is allelic withmi. Electron microscopic analysis of hair follicles and culturing of melanocytes from the skin of transgenic animals reveals an absence of cutaneous melanocytes in homozygotes and aberrant growth and morphology of the melanocytes isolated from hemizygous animals. The results presented here summarize the effects of this new allele of themi locus.