| First Author | Araki R | Year | 1997 |
| Journal | Proc Natl Acad Sci U S A | Volume | 94 |
| Issue | 6 | Pages | 2438-43 |
| PubMed ID | 9122213 | Mgi Jnum | J:39329 |
| Mgi Id | MGI:86712 | Doi | 10.1073/pnas.94.6.2438 |
| Citation | Araki R, et al. (1997) Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice. Proc Natl Acad Sci U S A 94(6):2438-43 |
| abstractText | The severe combined immune deficiency (SCID) mouse was reported as an animal model for human immune deficiency. Through the course of several studies, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) gene came to be considered a candidate for the SCID-responsible gene, We isolated an ORF of the murine DNA-PKcs gene from SCID mice and their parent strain C.B-17 mice and determined the DNA sequences. The ORF of the murine DNA-PKcs gene contained 4125-aa residues and bad 78.9% homology with the human DNA-PKcs gene. A particularly important finding is that a T to A transversion results in the substitution of termination codon in SCID mice for the Tyr-4046 in C.B-17 mice. No other mutation was detected in the ORF of the gene, The generality of this transversion was confirmed using four individual SCID and wild-type mice, The substitution took place in the phosphatidylinositol 3- kinase domain, and the mutated gene encodes the truncated products missing 83 residues of wild-type DNA-PKcs products. Furthermore, the quantity of DNA-PKcs transcript in wild-type and SCID cells was almost equal, These observations indicate that the DNA-PKcs gene is the SCID- responsible gene itself and that the detected mutation leads to the SCID aberration. |
