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Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat
- Source :
- Journal of Autoimmunity
- Publication Year :
- 2003
-
Abstract
- Peripheral T cell lymphopenia (lyp) in the BioBreeding (BB) rat is linked to a frameshift mutation in Ian5, a member of the Immune Associated Nucleotide (Ian) gene family on rat chromosome 4. This lymphopenia leads to type 1 (insulin-dependent) diabetes mellitus (T1DM) at rates up to 100% when combined with the BB rat MHC RT1 u/u genotype. In order, to better study the lymphopenia phenotype without possible confounding effects of diabetes or other autoimmune disease, we generated congenic F344.lyp rats by introgression of lyp on diabetes-resistant MHC RT1 lv1/lv1 F344 rats. Analysis of thymic CD4 and CD8 T lymphocytes revealed no difference in the percentage of CD4(-)CD8(+)and CD4(+)CD8(-)subsets in lyp/lyp compared to +/+ F344 rats. The same subsets was however dramatically reduced in blood (P=0.005), spleen (P=0.019) and mesenteric lymph nodes (MLN) (P0.0001). Compared to F344 +/+ rats double positive CD4(+)CD8(+)T cells were increased only in lyp/lyp spleen (P=0.034) while double negative CD4(-)CD8(-)were increased in thymus (P=0.033), spleen (P=0.012), MLN (P0.0001), and peripheral blood (P0.0001). There were no signs of inflammatory lesions in organs and tissues in F344.lyp/lyp rats examined at 120 days of age or older. We thus conclude that the lymphopenia phenotype was reconstituted by introgression of lyp on to F344 rats without subsequent development of organ-specific autoimmunity. The congenic F344.lyp rat should prove useful to dissect the mechanisms by which the Ian5 frameshift mutation affects T cell selection, differentiation and maturation without organ-specific autoimmunity.
- Subjects :
- medicine.medical_specialty
Lymphoid Tissue
T-Lymphocytes
Immunology
Congenic
Autoimmunity
Breeding
T-cell development
Major histocompatibility complex
medicine.disease_cause
Article
Leukocyte Count
Animals, Congenic
T-Lymphocyte Subsets
Internal medicine
Lymphopenia
medicine
Immunology and Allergy
Mesenteric lymph nodes
Animals
Genome
biology
Lymphocytopenia
BB rat
medicine.disease
Flow Cytometry
Physical Chromosome Mapping
Rats, Inbred F344
Rats
F344 rat
Endocrinology
medicine.anatomical_structure
Mutation
biology.protein
Insulitis
CD8
Biobreeding rat
Subjects
Details
- ISSN :
- 08968411
- Volume :
- 21
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of autoimmunity
- Accession number :
- edsair.doi.dedup.....cbde956a434a4e3da56d9a6f9cf0260d