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Journal of immunology (Baltimore, Md. : 1950)1997; 158(8); 3565-3569;

A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation.

Abstract: The equine SCID defect is more severe than its murine counterpart in that SCID foals are incapable of forming either coding or signal joints, whereas SCID mice manifest normal signal joint formation. To determine the basis of this difference and whether DNA-dependent kinase, catalytic subunit (DNA-PK(CS)), is involved in signal joint formation, equine DNA-PK(CS) transcripts were cloned and sequenced from normal and SCID cell lines. In the mutant allele, a frame-shift mutation truncates the protein N terminal of the domain with homology to the phosphatidylinositol 3-kinase family resulting in complete absence of full length DNA-PK(CS) and accounting for the kinase-negative phenotype of these cells; the mutation in SCID mice allows for some DNA-PK(CS) expression. The difference in DNA-PK(CS) expression in SCID mice and foals explains the more severe phenotype of equine SCID, and definition of DNA-PK(CS) as the defect in equine SCID demonstrates that DNA-PK(CS) is required for both coding and signal joint formation.
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Publication Date: 1997-04-15 PubMed ID: 9103416
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  • Journal Article
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  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research studied the role of the DNA-PK(CS) mutation in equine Severe Combined Immunodeficiency (SCID) and found it was responsible for the disorder’s severity, as it disrupts coding and signal joint formation – actions essential for immune system development.

Understanding the Context: Equine SCID and DNA-PK(CS)

  • The researchers examined Severe Combined Immunodeficiency (SCID) in horses. SCID is a disorder where the animal’s immune system development is incomplete, leaving them extremely vulnerable to infections.
  • This condition is particularly severe in horses, where foals suffering from SCID are incapable of forming coding and signal joints, key components of the body’s immune response.
  • The research team focused their attention on the DNA-dependent kinase, catalytic subunit (DNA-PK(CS)) – an enzyme previously linked to SCID in mice.

Technical Exploration: Sequencing and Mutation

  • The team cloned and sequenced equine DNA-PK(CS) transcripts from normal and SCID cell lines to understand the differences and potential mutations.
  • They found a frame-shift mutation in the mutant allele that truncates the protein N terminal of the domain with homology to the phosphatidylinositol 3-kinase family.
  • This mutation was found to cause a complete absence of full length DNA-PK(CS), accounting for the kinase-negative phenotype of these cells.
  • In contrast, the frame-shift mutation permits some level of DNA-PK(CS) expression in SCID mice.

The Role of DNA-PK CS in Equine SCID

  • The research identifies the DNA-PK CS mutation as the key factor contributing to the more severe phenotype of equine SCID compared to its murine counterpart.
  • This differential DNA-PK CS expression explains why SCID foals are unable to form coding and signal joints, therefore rendering them more susceptible to infections.
  • By pinpointing the key defect in equine SCID, researchers showed that DNA-PK CS is vital for coding and signal joint formation, thereby highlighting its significance for immune system development.

Implications and Conclusion

  • This research offers deep insights into equine SCID’s genetic underpinnings, potentially paving the way for new treatment methods for this debilitating condition.
  • Moreover, understanding the role of DNA-PK CS in immunodeficiency disorders can potentially help researchers address other similar conditions in different species.

Cite This Article

APA
Shin EK, Perryman LE, Meek K. (1997). A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation. J Immunol, 158(8), 3565-3569.

Publication

Journal of immunology (Baltimore, Md. : 1950)
ISSN: 0022-1767
NlmUniqueID: 2985117R
Country: United States
Language: English
Volume: 158
Issue: 8
Pages: 3565-3569

Researcher Affiliations

Shin, E K
  • Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Perryman, L E
    Meek, K

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Base Sequence
      • Cell Line
      • DNA-Activated Protein Kinase
      • DNA-Binding Proteins
      • Gene Rearrangement
      • Horses
      • Immunoglobulin Variable Region / genetics
      • Mice
      • Mice, SCID
      • Molecular Sequence Data
      • Mutation
      • Protein Serine-Threonine Kinases / genetics
      • Severe Combined Immunodeficiency / genetics
      • Signal Transduction / genetics

      Grant Funding

      • AI32600 / NIAID NIH HHS
      • SR01HL46651 / NHLBI NIH HHS

      Citations

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