| abstract |
The present invention provides mice whose PTP-1B gene has been disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein but appear physiologically normal. However, when fed a normal diet, the mice have half the circulating insulin levels as compared to their wild-type littermates. In the glucose tolerance test and the insulin tolerance test, the mice show increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show resistance to weight gain compared to their wild-type littermates. Also provided are methods for producing the mice and cell lines derived from the mice. The present invention also provides a method for identifying an inhibitor of the enzymatic activity of PTP-1B, and an inhibitor identified by such a method. |