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AssigneesMerck & Co., Inc., McGill University
InventorsBrian Kennedy, Paul Payette, Michael Gresser, Chidambaram Ramachandran, Michel Tremblay, Mounib Elchebly
Estimating the term…
The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.
A transgenic mouse whose genome is homozygous for a disrupted PTP-1B gene, such that said mouse has no detectable PTP-1B, and wherein said mouse exhibits increased insulin sensitivity as compared to wild-type mice.
A transgenic mouse whose genome is homozygous for a disrupted PTP-1B gene, such that said mouse has no detectable PTP-1B, and wherein said mouse exhibits resistance to diet induced obesity as compared to wild-type mice.
A transgenic mouse whose genome is homozygous for a disrupted PTP-1B gene, such that said mouse has no detectable PTP-1B, and wherein said mouse exhibits a phenotype selected from the group consisting of mice having about half the level of circulating insulin in the fed state as compared to wild-type mice, having about 13% of the level of blood glucose in the fed state as compared to wild-type mice and having about half the weight gain when fed a high fat, high carbohydrate diet as compared to wild-type mice.
A method of producing a mouse whose genome is homozygous for a disrupted PTP-1B gene, such that said mouse has no detectable PTP-1B, the method comprising:
A transgenic mouse whose genome is heterozygous for a disrupted PTP-1B gene, wherein said disrupted gene in a homozygous state produces a mouse that has no detectable PTP-1B, and wherein said mouse exhibits increased insulin sensitivity as compared to wild-type mice.
Dependencies are inferred from the claim text.