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

Daniel H Moralejo; Hyunhee A Park; Sara J Speros; Armand J MacMurray; Anne E Kwitek; Howard J Jacob; Eric S Lander; Åke Lernmark

doi:10.1016/S0896-8411(03)00138-0

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

Daniel H Moralejo, Hyunhee A Park, Sara J Speros, Armand J MacMurray, Anne E Kwitek, Howard J Jacob, Eric S Lander, Åke Lernmark

Celiac Disease and Diabetes Unit

Research output: Contribution to journal › Article › peer-review

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) (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

Original language	English
Pages (from-to)	315-324
Journal	Journal of Autoimmunity
Volume	21
Issue number	4
DOIs	https://doi.org/10.1016/S0896-8411(03)00138-0
Publication status	Published - 2003

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10.1016/S0896-8411(03)00138-0

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

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) (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",

author = "Moralejo, \{Daniel H\} and Park, \{Hyunhee A\} and Speros, \{Sara J\} and MacMurray, \{Armand J\} and Kwitek, \{Anne E\} and Jacob, \{Howard J\} and Lander, \{Eric S\} and {\AA}ke Lernmark",

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doi = "10.1016/S0896-8411(03)00138-0",

language = "English",

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T1 - Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat.

AU - Moralejo, Daniel H

AU - Park, Hyunhee A

AU - Speros, Sara J

AU - MacMurray, Armand J

AU - Kwitek, Anne E

AU - Jacob, Howard J

AU - Lander, Eric S

AU - Lernmark, Åke

PY - 2003

Y1 - 2003

N2 - 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

AB - 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

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DO - 10.1016/S0896-8411(03)00138-0

M3 - Article

SN - 0896-8411

VL - 21

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JF - Journal of Autoimmunity

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

Abstract

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