Title:
GENETICALLY MODIFIED RAT MODELS FOR CYTOKINE-CYTOKINE SIGNALING PATHWAYS
Document Type and Number:
WIPO Patent Application WO/2011/011678
Kind Code:
A3
Abstract:
The present invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in cytokine-cytokine mediated autoimmune and inflammatory disease. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human autoimmune and inflammatory disease and methods of their use. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a cytokine gene such as the Faslg gene, the Fas gene, etc. In one embodiment, the cytokine gene is the Faslg gene. In another embodiment, the cytokine gene is one of several known cytokine genes, such as Fas, IFNγ, TNF-α, IL-2, IL-10, and IL-12. The inactivation of at least one of these cytokine alleles results in an animal with a higher susceptibility to cytokine-cytokine mediated autoimmune and inflammatory disease induction. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for cytokine-cytokine mediated autoimmune and inflammatory disease and as a test animal for autoimmune and other studies.
Inventors:
OSTERTAG ERIC (US)
CRAWFORD JOHN STUART (US)
CRAWFORD JOHN STUART (US)
Application Number:
PCT/US2010/043043
Publication Date:
April 07, 2011
Filing Date:
July 23, 2010
Export Citation:
Assignee:
TRANSPOSAGEN BIOPHARMACEUTICALS INC (US)
OSTERTAG ERIC (US)
CRAWFORD JOHN STUART (US)
OSTERTAG ERIC (US)
CRAWFORD JOHN STUART (US)
International Classes:
C12N15/85; A01K67/027
Domestic Patent References:
| WO2010124200A2 | 2010-10-28 |
Other References:
PHYSGEN KNOCKOUT: "Strain Report for F344-Faslg Tn(sb-T2/Bart3)2.325Mcwi", 11 May 2009 (2009-05-11), XP002612681, Retrieved from the Internet [retrieved on 20101203]
NAGATA S.: "Human autoimmune lymphoproliferative syndrome, a defect in the apoptosis-inducing Fas receptor: a lesson from the mouse model.", J HUM GENET., vol. 43, no. 1, 1998, pages 2 - 8, XP002612682
FIELDS ML, NISH SA, HONDOWICZ BD, METZGAR MH, WHARTON GN, CATON AJ, ERIKSON J.: "The influence of effector T cells and Fas ligand on lupus-associated B cells.", J IMMUNOL., vol. 175, no. 1, 1 July 2005 (2005-07-01), pages 104 - 111, XP002612683
KITADA K, KENG VW, TAKEDA J, HORIE K.: "Generating mutant rats using the Sleeping Beauty transposon system.", METHODS., vol. 49, no. 3, 4 May 2009 (2009-05-04), pages 236 - 242, XP002612684
LU B, GEURTS AM, POIRIER C, PETIT DC, HARRISON W, OVERBEEK PA, BISHOP CE.: "Generation of rat mutants using a coat color-tagged Sleeping Beauty transposon system.", MAMM GENOME., vol. 18, no. 5, 8 June 2007 (2007-06-08), pages 338 - 346, XP002489198
SMITS B M G ET AL: "Rat genetics: the next episode", TRENDS IN GENETICS, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 22, no. 4, 1 April 2006 (2006-04-01), pages 232 - 240, XP025226192, ISSN: 0168-9525, [retrieved on 20060401], DOI: DOI:10.1016/J.TIG.2006.02.009
NAGATA S.: "Human autoimmune lymphoproliferative syndrome, a defect in the apoptosis-inducing Fas receptor: a lesson from the mouse model.", J HUM GENET., vol. 43, no. 1, 1998, pages 2 - 8, XP002612682
FIELDS ML, NISH SA, HONDOWICZ BD, METZGAR MH, WHARTON GN, CATON AJ, ERIKSON J.: "The influence of effector T cells and Fas ligand on lupus-associated B cells.", J IMMUNOL., vol. 175, no. 1, 1 July 2005 (2005-07-01), pages 104 - 111, XP002612683
KITADA K, KENG VW, TAKEDA J, HORIE K.: "Generating mutant rats using the Sleeping Beauty transposon system.", METHODS., vol. 49, no. 3, 4 May 2009 (2009-05-04), pages 236 - 242, XP002612684
LU B, GEURTS AM, POIRIER C, PETIT DC, HARRISON W, OVERBEEK PA, BISHOP CE.: "Generation of rat mutants using a coat color-tagged Sleeping Beauty transposon system.", MAMM GENOME., vol. 18, no. 5, 8 June 2007 (2007-06-08), pages 338 - 346, XP002489198
SMITS B M G ET AL: "Rat genetics: the next episode", TRENDS IN GENETICS, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 22, no. 4, 1 April 2006 (2006-04-01), pages 232 - 240, XP025226192, ISSN: 0168-9525, [retrieved on 20060401], DOI: DOI:10.1016/J.TIG.2006.02.009
Attorney, Agent or Firm:
ALBAINY-JENEI, Stephen, R. et al. (201 East Fifth Street2200 PNC Cente, Cincinnati OH, US)
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