Transgenic knockout mouse having functionally disrupted interleu

Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

800 13, 800 22, 800 25, 435 691, 4353201, 435325, 435463, 435455, 536 231, 536 232, C12N 500, C12N 1500, C07H 2104, A01K 67027

Patent

active

061004456

ABSTRACT:
A transgenic mouse 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 mouse may be heterozygous or, more preferably, homozygous for the ICE gene disruption. In homozygous mice, secretion of mature interleukin-1.beta. and interleukin-1.alpha. is substantially reduced relative to non-mutant mice. The mice of the invention can be used as positive controls to evaluate the efficacy of ICE inhibitors and to identify disease conditions that can be treated with ICE inhibitors. A transgenic mouse having functionally disrupted endogenous ICE genes but which has been reconstituted with a human ICE gene is also provided. This mouse can be used to identify agents that inhibit human ICE in vivo. Nucleic acid constructs for functionally disrupting an endogenous 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.

REFERENCES:
Li, et al, Cell, vol. 80, pp. 401-411, Feb. 10, 1995.
Houdebine, Journal of Biotechnology 34, pp. 269-287, May 1994.
Cerretti et al., Genomics 20, pp. 468-473, 1994.
Molineaux Proc. Natl. Acad. Sci. USA vol. 90, pp. 1809-1813, Mar. 1993.
Koshura, Proc. Natl. Acad. Sci. USA vol. 86. pp 5227-5231, Jul. 1989.
Webster's II New Riverside University Dictionary 1984 Houghton Mifflin Company.
Silver et al. 1985 Molecular and Cellular Biology 5(3): 518-528.
Capecchi, M., "The New Mouse Genetics: Altering the Genome by Gene Targeting," Trends in Genetics, vol. 5, No. 3, 70-76 (1989).
Medline Abstract No. 94360969, Erdo, F., et al., "Measurement of Interleukin-1 Liberation in Zymosan Air-pouch Exudate in Mice," Agents and Actions, vol. 41, No. 1-2, pp. 93-95 (1994).
Black, Roy A. et al. (1989) "Activation of interleukin-1.beta.by a co-induced protease" FEB 247(2): 386-390.
Black, Roy A. et al. (1989) "A Pre-aspartate-specific Protease from Human Leukocytes That Cleaves Pro-interleukin-1.beta." J. Biol. Chem. 264(10): 5323-5326.
Bradley, A. (1991) "Modifying the mammalian genome by gene targeting" Current Opinion in Biotechnology 2: 823-829.
Capecchi, M.R. (1989) "Altering the Genome by Homologous Recombination" Science 244: 1288-1292.
Casano, F.J. et al. (1994) "Structure and Complete Nucleotide Sequence of the Murine Gene Encoding Interleukin-1.beta. Converting Enzyme (ICE)" Genomics 20: 474-481.
Cerretti, D.P. et al. (1992) "Molecular Cloning of the Interleukin-1.beta. Converting Enzyme" Science 256: 97-100.
Fernandes-Alnemri, T. et al. (1994) "CPP32, a Novel Human Apoptotic Protein with Homology to Caenorhabditis elegans Cell Death Protein Ced-3 and Mammalian Interleukin-1.beta.-converting Enzyme" J. Biol. Chem. 269(49):30761-30764.
Kumar, S. et al. (1994) "Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1.beta.-converting enzyme" Genes & Development 8: 1613-1626.
Mansour, S.L. et al. (1988) "Disruption of the photo-oncogene int-2 in mouse embryo-derived stem cells; a general strategy for targeting mutations to non-selectable genes" Nature 336: 348-352.
Miura, M. et al. (1993) "Induction of Apoptosis in Fibroblasts by IL-1.beta.-Converting Enzyme, a Mammalian Homolog of the C. elegans Cell Death Gene ced-3" Cell 75: 653-660.
Nett, M.A. et al. (1992) "Molecular Cloning of the Murine IL-1.beta. Converting Enzyme cDNA" J. Immunol. 149(10): 3254-3259.
Thornberry, N.A. et al. (1992) "A novel heterodimeric cysteine protease is required for interleukin-1.beta. processing in monocytes" Nature 356: 768-774.
Walker, N.P.C. et al. (1994) "Crystal Structure of the Cysteine Protease Interleukin-1.beta.-Converting Enzyme: A (p20/p10).sub.2 Homodimer" Cell 78: 343-352.
Wang, L. et al. (1994) "Ich-1, an Ice/ced-3-Related Gene, Encodes Both Positive and Negative Regulators of Programmed Cell Death" Cell 78: 739-750.
Wilson, K.P. et al. (1994) "Structure and mechanism of interleukin-1.beta. converting enzyme" Nature 370: 270-275.
Yuan, J. et al. (1993) "The C. elegans Cell Death Gene ced-3 Encodes a Protein Similar to Mammalian Interleukin-1.beta.-Converting Enzyme" Cell 75: 641-652.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Transgenic knockout mouse having functionally disrupted interleu does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Transgenic knockout mouse having functionally disrupted interleu, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transgenic knockout mouse having functionally disrupted interleu will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-1151671

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.