TRANSGENIC NONHUMAN ANIMAL HAVING FUNCTIONALLY DISRUPTED INTERLEUKIN-1.BETA. CONVERTING ENZYME GENE

摘要

A transgenic nonhuman animal having somatic and germ cells in which at least one allele of an endogenous interleukin-1.beta. converting enzyme (ICE) gene is functionally disrupted is provided. The animal may be heterozygous or, mo re preferably, homozygous for the ICE gene disruption and is preferably a mouse . In homozygous animals, secretion of mature interleukin-1.beta. and interleuk in- 1.alpha. is substantially reduced relative to non-mutant animals. The animal s of the invention can be used as positive controls to evaluate the efficacy o f ICE inhibitors and to identify disease conditions that can be treated with I CE inhibitors. A transgenic nonhuman animal having functionally disrupted endogenous ICE genes but which has been reconstituted with a human ICE gene is also provided. This animal can be used to identify agents that inhibit human ICE in vivo. Nucleic acid constructs for functionally disrupting an endogeno us ICE gene in a host cell, recombinant vectors including the nucleic acid construct, and host cells into which the nucleic acid construct has been introduced are also encompassed by the invention.