The endogenous locus was replaced with an nls-lacZ-SV40 poly(A) gene, leaving the original splice acceptor site and translational start in place, as well as the 3' homologous region right after the TAG stop codon, unaltered. An FRT flanked HPRT gene was placed in front of the 3' homologous region in the reverse orientation. The HPRT gene was removed by Flp mediated recombination. Western blot analysis confirmed the absence of protein expression in the brains of homozygous mice. LacZ expression was confirmed in Schwann cells, oligodendrocytes and Bergmann glia cells.