Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat.

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) (P<0.0001). Compared to F344 +/+ rats double positive CD4(+)CD8(+)T cells were increased only in lyp/lyp spleen (P=0.034) while double n

Park, Hyunhee A (author)
Speros, Sara J (author)
MacMurray, Armand J (author)
Kwitek, Anne E (author)
Jacob, Howard J (author)
Lander, Eric S (author)
Lernmark, ÅkeLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups(Swepub:lu)endo-ale (author)
Celiaki och diabetesForskargrupper vid Lunds universitet (creator_code:org_t)

By the author/editor: Moralejo, Daniel ...; Park, Hyunhee A; Speros, Sara J; MacMurray, Arman ...; Kwitek, Anne E; Jacob, Howard J; show more...; Lander, Eric S; Lernmark, Åke; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

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