In vivo models for rabGEF1-dependent signaling and functions
US7365239B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Jun 21, 2005 |
| Grant date | Apr 29, 2008 |
| Priority date | — |
| Expiry date | Sep 9, 2025 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N2517/02
- WIPO fieldOther special machines
- WIPO sectorMechanical engineering
Abstract
Non-human transgenic animal models and cells derived therefrom are provided for RabGEF1 function. RabGEF1 is a negative regulator of FcεRI-dependent mast cell activation and T cell activation via the T cell receptor and a lack of RabGEF1 results in the development of skin inflammation in vivo. The mast cells derived from such animals exhibit enhanced Ras-mediated signaling and functional responses when activated through high affinity IgE receptors. These cells show significant potentiation of IgE and antigen-dependent secretion of 3 classes of mast cell mediators, providing a useful source of mast cells for screening assays. The animals and cells derived therefrom are also useful for screening biologically active agents that may modulate RabGEF1 function, including therapeutic agents for the treatment of skin disorders, such as eczema, psoriasis, and the like, or for the treatment of other mast cell-associated disorders, including allergic disorders, such as asthma and hay fever, and certain autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis. Inhibiting RabGEF1 function may be useful in those conditions in which it is desirable to enhance T cell and/or mast c…
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