Transgene copy number-dependent rescue of murine β-globin knockout mice carrying a 183 kb human β-globin BAC genomic fragment

Abstract

We report the generation and characterisation of the first transgenic mice exclusively expressing normal human β-globin (huβ-globin) from a 183 kb genomic fragment. Four independent lines were generated, each containing 2-6 copies of the huβ-globin locus at a single integration site. Steady state levels of huβ-globin protein were dependent on transgene copy number, but independent of the site of integration. Hemizygosity for the transgene on a heterozygous knockout background ( huβ+/0, muβth-3/+) complemented fully the hematological abnormalities associated with the heterozygous knockout mutation in all four lines. Importantly, the rescue of the embryonic lethal phenotype that is characteris..