Phenotypes Associated with This Genotype

Genotype
MGI:3040589

• Allelic Composition: Sigirr^tm1Mant/Sigirr^tm1Mant
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

immune system

immune system phenotype ( J:88907 )

N • homozygotes display normal inflammatory reactions in tissues outside the gastrointestinal tract, including normal peritoneal inflammation to thioglycollate and normal systemic or local inflammation in response to LPS

increased susceptibility to induced colitis ( J:88907 )

• in response to dextran sodium sulfate (DSS)-induced acute colitis, homozygotes exhibit greater blood loss but only a non-significant increase in body weight loss relative to wild-type controls

• in response to DSS-induced chronic colitis, homozygotes display a significant increase in weight loss and intestinal bleeding, more severe damage of intestinal mucosa, a higher degree of erosion and inflammatory cell recruitment, and an increased number of gross focal ulcerations relative to wild-type control mice

abnormal dendritic cell physiology ( J:88907 )

• mutant bone marrow-derived dendritic cells (DCs) display a significant increase in cytokine secretion in response to different concentrations of Toll-like receptor (TLR) agonists (LPS or CpG oligodeoxynucleotides) relative to wild-type DCs

abnormal chemokine secretion ( J:88907 )

• mutant bone marrow-derived DCs display a significant increase in CXCL10 production in response to different concentrations of LPS (10 or 100 ng/ml LPS) and to different concentrations of bacterial CpG oligodeoxynucleotide motif GACGTT (0.2 or 2 g/ml CpG 1826) relative to wild-type DCs

abnormal interleukin secretion ( J:88907 )

• mutant bone marrow-derived DCs display a significant increase in IL-6, IL-10 and IL-12 secretion in response to different concentrations of LPS or CpG 1826

increased interleukin-6 secretion ( J:88907 )

• mutant bone marrow-derived DCs display a significant increase in IL-6 production in response to different concentrations of LPS (10 or 100 ng/ml LPS) and to 0.2 g/ml (but not 0.02 g/ml) of bacterial CpG 1826 relative to wild-type DCs

• however, mutant bone marrow-derived DCs show no significant differences in IL-6 production in response to 10 or 100 g/ml of Candida albicans or to 5 or 50 g/ml of poly(I)-(C) relative to wild-type DCs

• unlike bone marrow-derived DCs, mutant thioglycollate-elicited peritoneal macrophages exhibit normal IL-6 secretion in response to 100 ng/ml LPS relative to wild-type controls

digestive/alimentary system

increased susceptibility to induced colitis ( J:88907 )

• in response to dextran sodium sulfate (DSS)-induced acute colitis, homozygotes exhibit greater blood loss but only a non-significant increase in body weight loss relative to wild-type controls

• in response to DSS-induced chronic colitis, homozygotes display a significant increase in weight loss and intestinal bleeding, more severe damage of intestinal mucosa, a higher degree of erosion and inflammatory cell recruitment, and an increased number of gross focal ulcerations relative to wild-type control mice