The Ptpn11 binding domain, encoded by sequence in exon 17, was disrupted by homologous recombination of a construct containing missense mutations at codons 757 (tyrosine to phenylalanine) and 760 (valine to alanine). Furthermore, an IRES-neo cassette was inserted into the 3' region of exon 17. A biochemical assay of liver tissue showed that the Il6st mediated signalling pathway was disrupted in mutant mice.