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AssigneePresident and Fellows of Harvard College
InventorsWei Zhang, Jonathan G. Seidman, Usamah S. Kagyali, Huntington Potter
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The present invention relates to a method of identifying drugs or agents which have immuno-suppressive effects through or as a result of their effect on calcineurin, including drugs which affect the calcineurin Aα (CNAα) subunit or the calcineurin Aβ (CNAβ) subunit. In addition, the present invention relates to a method of identifying drugs which reduce (partially or totally) phosphorylation of the microtubule-associated protein tau, in the nervous system of a mammal; a method of identifying drugs which reduce (partially or totally) paired helical filament formation in the nervous system of a mammal; and a method of identifying drugs which reduce (partially or totally) formation of paired helical filaments, amyloid deposits or both. The present invention also relates to transgenic non-human mammals, such as rodents and particularly mice, which lack a functional calcineurin gene and, thus, have disyrupted calcineurin expression.
A method of identifying an agent that reduces the phosphorylation of tau protein in the nervous system of a mammal, comprising the steps of:
A Transgenic mouse whose genome comprises a genetically engineered homozygous disruption of the endogenous calcineurin A α isoform (CNAα) gene, wherein no functional CNAα is produced by said mouse, and wherein said mouse exhibits a phenotype of defects in Υ cell immunity, ataxia, seizures, weight loss, reduced life expectancy and accumulation of endogenous phosphorylated tau protein.
A method of making a transgenic mouse whose genome comprises a genetically engineered homozygous disruption of the endogenous calcineurin A α isoform (CNAα) gene, wherein no functional CNAα is produced by said mouse, and wherein said mouse exhibits a phenotype of defects in Υ cell immunity, ataxia, seizures, weight loss, reduced life expectancy and accumulation of endogenous phosphorylated tau protein comprising, p1 a) introducing a targeting vector into embryonic stem cells thereby producing a transgenic embryonic stem cell comprising a disrupted CNAα gene, p1 b) introducing said embryonic stem cell into a blastocyst;
Dependencies are inferred from the claim text.