Molecular pathology of severe combined immunodeficiency in mice, horses, and dogs.
Abstract: Severe combined immunodeficiency (SCID) is an inherited disorder of humans, mice, horses, and dogs, in which affected individuals are incapable of generating antigen-specific immune responses. It occurs when lymphocyte precursors fail to differentiate into mature lymphocytes because of mutations within recombinase-activating genes 1 and 2 or within the genes encoding deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK). It also occurs when differentiated lymphocytes are incapable of completing signal transduction pathways because of defects in cell surface receptors for interleukins (IL). A spontaneous mutation in DNA-PKcs of BALB/c mice results in SCID, as do experimentally induced mutations in RAG1 and RAG2. SCID in horses results from a spontaneous mutation in DNA-PKcs. Two molecular mechanisms account for SCID in dogs. Jack Russell Terriers have a mutation within the DNA-PKcs gene, whereas Cardigan Welsh Corgi and Basset Hound have different defects in the gene encoding the gamma chain that is common to the receptors for IL-2, -4, -7, -9, -15, and -21. The location of the mutation within target genes influences the spectrum of diseases observed in affected animals.
Publication Date: 2004-03-16 PubMed ID: 15017021DOI: 10.1354/vp.41-2-95Google Scholar: Lookup
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Summary
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This research article investigates the molecular causes of severe combined immunodeficiency (SCID) in different animals including mice, horses, and dogs, revealing that the disorder occurs due to mutations within certain genes that hampers normal immune responses.
Understanding Severe Combined Immunodeficiency (SCID)
- SCID is an inherited disorder that impacts the immune system.
- It affects humans, mice, horses, and dogs, making them incapable of generating specific immune responses.
- The disorder comes into play when lymphocyte precursors, which should naturally develop into mature lymphocytes, fail to do so.
- This failure is attributed to mutations within certain genes, namely, recombinase-activating genes 1 and 2 (RAG1 and RAG2) or genes encoding DNA-dependent protein kinase (DNA-PK).
- Another way SCID manifests is when mature lymphocytes cannot complete signal transduction pathways due to defects in cell surface receptors for interleukins (IL), crucial proteins that regulate the immune system.
Role of Different Genes in SCID Formation
- A spontaneous mutation in the DNA-PKcs of a BALB/c mice type results in SCID which is similar to the situational occurrence when experimentally induced mutations in RAG1 and RAG2 are present.
- Spontaneous mutation in DNA-PKcs is also the causes SCID in horses.
Types of Mutations Causing SCID in Different Dogs
- The research discovered two molecular mechanisms that lead to SCID in dogs, with each related to a particular breed.
- In Jack Russell Terriers, a mutation within the DNA-PKcs gene causes the disorder.
- Conversely, Cardigan Welsh Corgi and Basset Hound breeds have different defects in the gene encoding the gamma chain common to the receptors for several interleukins; specifically IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.
Effect of Mutation Location Within Target Genes
- The location of the mutation within the target genes (RAG1, RAG2, or DNA-PKcs) significantly influences the range of diseases that can manifest in the affected animals.
Cite This Article
APA
Perryman LE.
(2004).
Molecular pathology of severe combined immunodeficiency in mice, horses, and dogs.
Vet Pathol, 41(2), 95-100.
https://doi.org/10.1354/vp.41-2-95 Publication
Researcher Affiliations
- College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1601, USA. lance.perryman@colostate.edu.
MeSH Terms
- Animals
- DNA-Activated Protein Kinase
- DNA-Binding Proteins
- Dog Diseases / genetics
- Dogs
- Genes, RAG-1 / genetics
- Genes, Recessive / genetics
- Horse Diseases / genetics
- Horses
- Immunoglobulin gamma-Chains / genetics
- Lymphocytes / pathology
- Mice
- Mutation / genetics
- Protein Serine-Threonine Kinases / genetics
- Rodent Diseases / genetics
- Severe Combined Immunodeficiency / genetics
- Severe Combined Immunodeficiency / veterinary
- Signal Transduction / genetics
Citations
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