CA mice were generated by replacing the adult mouse β globin genes with a human γHPFHδβ0 globin gene cassette in mouse ES cells. (A) Scheme of targeted gene replacement of the adult mouse β globin genes by a human γHPFHδβ0 globin gene cassette in mouse ES cells. The hyg marker gene was deleted by breeding to CRE recombinase transgenic mice.20 (B) Southern blot confirmation of correct homologous recombination. The 5′ probe hybridizes with a 9.2-kb XbaI fragment from the wild-type allele and a 7.9-kb fragment from the human globin KI allele. The 3′ probe derived from part of the βmin globin gene anneals to a 14.8-kb EcoRI fragment from the βmin globin gene, a 7.3-kb fragment from the βmaj globin gene, and a 10.3-kb fragment from the human globin KI allele.