| First Author | Poltorak A | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 4 | Pages | 2106-11 |
| PubMed ID | 11489994 | Mgi Jnum | J:70821 |
| Mgi Id | MGI:2148358 | Doi | 10.4049/jimmunol.167.4.2106 |
| Citation | Poltorak A, et al. (2001) A point mutation in the il-12rbeta2 gene underlies the il-12 unresponsiveness of lps-defective c57bl/10sccr mice. J Immunol 167(4):2106-11 |
| abstractText | Lps-defective C57BL/10ScCr (Cr) mice are homozygous for a deletion encompassing Toll-like receptor 4 that makes them refractory to the biological activity of LPS. In addition, these mice exhibit an inherited IL-12 unresponsiveness resulting in impaired IFN-gamma responses to different microorganisms. By positional cloning methods, we show here that this second defect of Cr mice is due to a mutation in a single gene located on mouse chromosome 6, in close proximity to the Igkappa locus. The gene is IL-12Rbeta2. Cr mice carry a point mutation creating a stop codon that is predicted to cause premature termination of the translated IL-12Rbeta2 after a lysine residue at position 777. The truncated beta2 chain can still form a heterodimeric IL-12R that allows phosphorylation of Janus kinase 2, but, unlike the wild-type IL-12R, can no longer mediate phosphorylation of STAT4. Because the phosphorylation of STAT4 is a prerequisite for the IL-12-mediated induction of IFN-gamma, its absence in Cr mice is responsible for their defective IFN-gamma response to microorganisms. |
