Tyrosine 1138 was 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 this tyrosine with phenylalanine abolished leptin stimulated STAT3 phosphorylation in the hypothalamus. (J:142218)