A G to T transversion at bp 923 in exon 10 resulting in the substitution of a valine for a glycine at amino acid 308 (G308V) was introduced via homologous recombination. Targeting took place in ES cells homozygous for the Tg(Prm-cre)70Og transgene, which expresses Cre recombinase in male germ cells. A floxed neo cassette inserted into intron 11 during homologous recombination in ES cells was subsequently excised by Cre-mediated recombination upon transmission from male chimeric mice. RT-PCR confirmed that RNA expression is normal however western blot analysis demonstrated that protein expression was absent in the liver and almost absent in the ileum.