All Phenotypes Rnf20<Gt(RRJ249)Byg> MGI Mouse

increased susceptibility to induced colitis ( J:268221 )

• heterozygotes develop more severe colon inflammation than wild-type controls by day 7 after dextran sodium sulfate (DSS, 2%) treatment; although inflammation is partially attenuated from day 65 onward, colonoscopy score is still higher than that in wild-type controls at day 180, indicating that heterozygotes are prone to both acute and chronic DSS-induced colonic inflammation

• DSS-treated heterozygotes show more abundant immune patches consisting of T cells, B cells and macrophages in their colons at day 65; more infiltrating macrophages (F4/80+), including M2 macrophages (CD206+), and more T cells (CD3+) are found at day 26 and 65 after DSS treatment

• inflamed colons from DSS-treated heterozygotes show stronger nuclear p65 staining and more abundant nuclear gamma-H2AX foci indicating, respectively, increased NF-kappa activity and DNA damage

enlarged spleen ( J:268221 )

• augmented splenomegaly at day 26 after DSS treatment

increased spleen weight ( J:268221 )

• increased spleen weight at day 26 and persisting up to day 180 after DSS treatment

abnormal leukocyte physiology ( J:268221 )

• myeloid-derived suppressor cells (MDSCs) from DSS-treated heterozygotes are more active, producing excessive reactive oxygen species (ROS) and nitric oxide (NO) and overexpressing arginase 1, and have a greater capacity to downregulate T cell receptor zeta chain levels in co-incubated naive T cells

abnormal T cell physiology ( J:268221 )

• splenic T cells from DSS-treated heterozygotes show downregulation of CD247 (T cell receptor zeta chain) within CD3+ cells, indicating impaired T cell function

• however, CD3 epsilon within CD3+ cells is normal, suggesting that reduced T cell functionality is mediated by MDSCs

increased interferon-gamma secretion ( J:268221 )

• increased IFN-gamma secretion from thioglycollate-elicited peritoneal inflammatory leukocytes and bone marrow-derived macrophages after treatment with TNF-alpha

increased tumor necrosis factor secretion ( J:268221 )

• increased TNF-alpha secretion from thioglycollate-elicited peritoneal inflammatory leukocytes and bone marrow-derived macrophages after treatment with TNF-alpha

increased large intestine adenocarcinoma incidence ( J:268221 )

• heterozygotes treated with AOM + DSS develop more polyps than similarly treated wild-type controls; adenomas often progress to carcinoma by day 180 after AOM + DSS treatment, unlike in wild-type controls

increased colon adenocarcinoma incidence ( J:268221 )

• several heterozygotes treated with DSS alone develop carcinomas by day 180 post-treatment, unlike DSS-treated wild-type controls

• some DSS-treated heterozygotes develop mucinous carcinoma with neoplastic glands invading the submucosa and penetrating the muscularis propria (T2 tumor stage), indicating an aggressive course

increased incidence of tumors by chemical induction ( J:268221 )

• heterozygotes injected with azoxymethane (AOM, 1 mg/g body weight) 7 days prior to DSS exposure develop more colorectal tumors than similarly treated wild-type controls

increased susceptibility to weight loss ( J:268221 )

• increased weight loss in response to DSS treatment

enlarged spleen ( J:268221 )

• augmented splenomegaly at day 26 after DSS treatment

increased spleen weight ( J:268221 )

• increased spleen weight at day 26 and persisting up to day 180 after DSS treatment

enlarged spleen ( J:268221 )

• augmented splenomegaly at day 26 after DSS treatment

increased spleen weight ( J:268221 )

• increased spleen weight at day 26 and persisting up to day 180 after DSS treatment

increased myeloid cell number ( J:268221 )

• DSS-treated heterozygotes have significantly more myeloid-derived suppressor cells (MDSCs) than wild-type controls at day 26 after DSS treatment, as determined by IHC staining and FACS analysis of CD11b/GR1 positive cells

abnormal leukocyte physiology ( J:268221 )

• myeloid-derived suppressor cells (MDSCs) from DSS-treated heterozygotes are more active, producing excessive reactive oxygen species (ROS) and nitric oxide (NO) and overexpressing arginase 1, and have a greater capacity to downregulate T cell receptor zeta chain levels in co-incubated naive T cells

abnormal T cell physiology ( J:268221 )

• splenic T cells from DSS-treated heterozygotes show downregulation of CD247 (T cell receptor zeta chain) within CD3+ cells, indicating impaired T cell function

• however, CD3 epsilon within CD3+ cells is normal, suggesting that reduced T cell functionality is mediated by MDSCs

abnormal nitric oxide homeostasis ( J:268221 )

• myeloid-derived suppressor cells (MDSCs) from DSS-treated heterozygotes produce excessive nitric oxide

increased incidence of tumors by chemical induction ( J:268221 )

• heterozygotes injected with azoxymethane (AOM, 1 mg/g body weight) 7 days prior to DSS exposure develop more colorectal tumors than similarly treated wild-type controls

oxidative stress ( J:268221 )

• MDSCs from DSS-treated mice produce excessive reactive oxygen species (ROS)

decreased colon length ( J:268221 )

• shorter colons at day 65 and persisting up to day 180 after DSS treatment

increased large intestine adenocarcinoma incidence ( J:268221 )

• heterozygotes treated with AOM + DSS develop more polyps than similarly treated wild-type controls; adenomas often progress to carcinoma by day 180 after AOM + DSS treatment, unlike in wild-type controls

increased colon adenocarcinoma incidence ( J:268221 )

• several heterozygotes treated with DSS alone develop carcinomas by day 180 post-treatment, unlike DSS-treated wild-type controls

• some DSS-treated heterozygotes develop mucinous carcinoma with neoplastic glands invading the submucosa and penetrating the muscularis propria (T2 tumor stage), indicating an aggressive course

abnormal intestine physiology ( J:268221 )

• increased fluorescence in the blood of mice force fed FITC-dextran, indicating compromised barrier function in the colon (intestinal leakiness)

increased susceptibility to induced colitis ( J:268221 )

• heterozygotes develop more severe colon inflammation than wild-type controls by day 7 after dextran sodium sulfate (DSS, 2%) treatment; although inflammation is partially attenuated from day 65 onward, colonoscopy score is still higher than that in wild-type controls at day 180, indicating that heterozygotes are prone to both acute and chronic DSS-induced colonic inflammation

• DSS-treated heterozygotes show more abundant immune patches consisting of T cells, B cells and macrophages in their colons at day 65; more infiltrating macrophages (F4/80+), including M2 macrophages (CD206+), and more T cells (CD3+) are found at day 26 and 65 after DSS treatment

• inflamed colons from DSS-treated heterozygotes show stronger nuclear p65 staining and more abundant nuclear gamma-H2AX foci indicating, respectively, increased NF-kappa activity and DNA damage

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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