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Proceedings of the National Academy of Sciences of the United States of America1995; 92(25); 11485-11489; doi: 10.1073/pnas.92.25.11485

Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity.

Abstract: V(D)J rearrangement is the molecular mechanism by which an almost infinite array of specific immune receptors are generated. Defects in this process result in profound immunodeficiency as is the case in the C.B-17 SCID mouse or in RAG-1 (recombination-activating gene 1) or RAG-2 deficient mice. It has recently become clear that the V(D)J recombinase most likely consists of both lymphoid-specific factors and ubiquitously expressed components of the DNA double-strand break repair pathway. The deficit in SCID mice is in a factor that is required for both of these pathways. In this report, we show that the factor defective in the autosomal recessive severe combined immunodeficiency of Arabian foals is required for (i) V(D)J recombination, (ii) resistance to ionizing radiation, and (iii) DNA-dependent protein kinase activity.
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Publication Date: 1995-12-05 PubMed ID: 8524788PubMed Central: PMC40426DOI: 10.1073/pnas.92.25.11485Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • 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 article investigates severe combined immunodeficiency (SCID) in Arabian foals, demonstrating that the condition is due to defects in immune receptor generation and DNA repair processes. Both these functions depend on a key factor that the foals lack.

About the Study

  • The researchers focus on the condition known as severe combined immunodeficiency (SCID), particularly as it manifests in Arabian horse foals. SCID is a genetic disease that affects the immune system, reducing the body’s ability to fight off infections.
  • The team posits that this condition in Arabian foals could be connected to issues with V(D)J recombination and DNA-dependent protein kinase activity.

V(D)J Recombination

  • V(D)J recombination is a molecular procedure responsible for generating the vast array of specific immune receptors in organisms.
  • Problems with this step can lead to significant immunodeficiency, as observed in the C.B-17 SCID mouse or in mice that are deficient in recombination-activating genes (RAG-1 or RAG-2).
  • The research indicates that the V(D)J recombinase, which carries out the V(D)J recombination process, likely comprises lymphoid-specific factors and more generally expressed components of the DNA double-strand break repair pathway.

Deficiency in DNA-Dependent Protein Kinase Activity

  • DNA-dependent protein kinase activity is vital in the DNA repair process. Any issues with this activity can lead to failures in DNA repair, which could affect the overall health of the organism.
  • The study claims that the factor deficient in Arabian foals with SCID is required for both V(D)J recombination and DNA repair mechanisms, indicating a possible cause of the condition.

Resistance to Ionizing Radiation

  • The study also indicates that the factor in question is necessary for resistance to ionizing radiation, suggesting that its deficiency could render organisms more susceptible to the harmful effects of such radiation.

In summary, this research sheds light on the multifaceted role of the deficient factor in Arabian foals, linking its absence to a series of physiological issues, including ineffective immune response, reduced DNA repair capabilities, and lowered resistance to ionizing radiation. The findings offer key insights into the understanding of SCID in Arabian foals and potentially similar immune conditions in other creatures.

Cite This Article

APA
Wiler R, Leber R, Moore BB, VanDyk LF, Perryman LE, Meek K. (1995). Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity. Proc Natl Acad Sci U S A, 92(25), 11485-11489. https://doi.org/10.1073/pnas.92.25.11485

Publication

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 92
Issue: 25
Pages: 11485-11489

Researcher Affiliations

Wiler, R
  • Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Leber, R
    Moore, B B
      VanDyk, L F
        Perryman, L E
          Meek, K

            MeSH Terms

            • Animals
            • Base Sequence
            • CHO Cells
            • Cell Line
            • Cricetinae
            • DNA Nucleotidyltransferases / genetics
            • DNA-Activated Protein Kinase
            • DNA-Binding Proteins
            • Fibroblasts / radiation effects
            • Gene Rearrangement
            • Genes, Recessive
            • Homeodomain Proteins
            • Horse Diseases / genetics
            • Horses
            • Immunoblotting
            • Mice
            • Mice, SCID / genetics
            • Molecular Sequence Data
            • Phenotype
            • Polymerase Chain Reaction
            • Protein Serine-Threonine Kinases / genetics
            • Proteins / genetics
            • Radiation Tolerance / genetics
            • Recombination, Genetic
            • Severe Combined Immunodeficiency / genetics
            • Severe Combined Immunodeficiency / veterinary
            • VDJ Recombinases

            Grant Funding

            • R01 AI048758 / NIAID NIH HHS
            • 5R01HL46651 / NHLBI NIH HHS
            • AI32600 / NIAID NIH HHS

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