Three tyrosine residues in exon 18 (985, 1077, 1138) were replaced with phenylalanine and a floxed neo cassette was inserted after exon 18 via homologous recombination. The floxed neo cassette was then removed by cre mediated recombination leaving behind a single loxP site. Quantitative RT-PCR indicated that expression of the long isoform in the hypothalamus of homozygotes was similar to that in wild-type mice. Replacement of these tyrosines with phenylalanines abolished leptin stimulated STAT3 phosphorylation in the hypothalamus. (J:142218)