Targeted Disruption of the Catalytic Subunit of the DNA-PK Gene in Mice Confers Severe Combined Immunodeficiency and Radiosensitivity

Guillermo E. Taccioli; Aldo G Amatucci; Heather Beamish; David A. Gell; Xie Xiang; Maria I.Torres Arzayus; Ann Priestley; Stephen P. Jackson; Ann Marshak Rothstein; Penny A. Jeggo; Victoria L. M. Herrera

doi:10.1016/s1074-7613(00)80618-4

Abstract

The DNA-dependent protein kinase is a mammalian protein complex composed of Ku70, Ku80, and DNA-PKcs subunits that has been implicated in DNA double-strand break repair and V(D)J recombination. Here, by gene targeting, we have constructed a mouse with a disruption in the kinase domain of DNA-PKcs, generating an animal model completely devoid of DNA-PK activity. Our results demonstrate that DNA-PK activity is required for coding but not for signal join formation in mice. Although our DNA-PKcs defective mice closely resemble Scid mice, they differ by having elevated numbers of CD4+CD8+ thymocytes. This suggests that the Scid mice may not represent a null phenotype and may retain some residual DNA-PKcs function.

Keywords

BiologyKu70Ku80Molecular biologyDNAGeneDNA-PKcsProtein subunitDNA repairSevere combined immunodeficiencyProtein kinase AProtein kinase domainKinaseCell biologyGeneticsDNA-binding proteinMutantTranscription factor

MeSH Terms

AnimalsB-LymphocytesCatalysisCell DifferentiationCellsCulturedDNA-Activated Protein KinaseDNA-Binding ProteinsEmbryoMammalianFibroblastsGene TargetingGenesT-Cell ReceptorImmunoglobulinsMiceMiceInbred C57BLMiceTransgenicProtein Serine-Threonine KinasesProtein StructureTertiaryRadiation ToleranceRecombinationGeneticSevere Combined ImmunodeficiencyT-Lymphocytes

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Publication Info

Year: 1998
Type: article
Volume: 9
Issue: 3
Pages: 355-366
Citations: 324
Access: Closed

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APA Style

                            
                                
                                    Guillermo E. Taccioli, 
                                
                                    Aldo G Amatucci, 
                                
                                    Heather Beamish
                                
                                et al.
                            
                            (1998). 
                            Targeted Disruption of the Catalytic Subunit of the DNA-PK Gene in Mice Confers Severe Combined Immunodeficiency and Radiosensitivity. 
                            Immunity
                            , 9
                            (3)
                            , 355-366.
                            https://doi.org/10.1016/s1074-7613(00)80618-4
                        

Identifiers

DOI: 10.1016/s1074-7613(00)80618-4
PMID: 9768755

Data Quality

Data completeness: 86%