DOI: 10.1073/pnas.94.6.2438. Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice

Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice

10.1073/pnas.94.6.2438

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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 4128-aa residues and had 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.

Bibliography

Araki, R., Fujimori, A., Hamatani, K., Mita, K., Saito, T., Mori, M., Fukumura, R., Morimyo, M., Muto, M., Itoh, M., Tatsumi, K., & Abe, M. (1997). Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiencyâmice. Proceedings of the National Academy of Sciences, 94(6), 2438â2443.

Authors 12

Ryoko Araki (first)
Akira Fujimori (additional)
Kiyohiro Hamatani (additional)
Kazuei Mita (additional)
Toshiyuki Saito (additional)
Masahiko Mori (additional)
Ryutaro Fukumura (additional)
Mitsuoki Morimyo (additional)
Masahiro Muto (additional)
Masahiro Itoh (additional)
Kouichi Tatsumi (additional)
Masumi Abe (additional)

References 37 Referenced 144

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M G Kim, W Schuler, M J Bosma, K B Marcu J Immunol 141, 1341–1347 (1988). (10.4049/jimmunol.141.4.1341) / J Immunol by Kim M G (1988)
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K Okazaki, S Nishikawa, H Sakano J Immunol 141, 1348–1352 (1988). (10.4049/jimmunol.141.4.1348) / J Immunol by Okazaki K (1988)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:09 a.m.)
Indexed	2 months ago (June 27, 2025, 10:02 a.m.)
Issued	28 years, 5 months ago (March 18, 1997)
Published	28 years, 5 months ago (March 18, 1997)
Published Online	28 years, 5 months ago (March 18, 1997)
Published Print	28 years, 5 months ago (March 18, 1997)

Funders 0

None

BibTeX

@article{Araki_1997, title={Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.6.2438}, DOI={10.1073/pnas.94.6.2438}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Araki, Ryoko and Fujimori, Akira and Hamatani, Kiyohiro and Mita, Kazuei and Saito, Toshiyuki and Mori, Masahiko and Fukumura, Ryutaro and Morimyo, Mitsuoki and Muto, Masahiro and Itoh, Masahiro and Tatsumi, Kouichi and Abe, Masumi}, year={1997}, month=mar, pages={2438–2443} }

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