Phenotypes for Map3k7 Tg(Lck-cre)1Jtak MGI:5823990 MGI Mouse

abnormal intestinal epithelium physiology ( J:238318 )

• increase in intestinal epithelial permeability indicating defective barrier function

colitis ( J:238318 )

• mice develop spontaneous colitis

• mice in which gut commensal bacteria is removed by treatment with four antibiotics do not exhibit colitis

• -6-8 week old mutants transferred with TCRalphabeta+CD8alpha+ IELS show significant amelioration of colitis, however transfer with CD8+ T or natural killer cells has no effect on colitis

abnormal T cell morphology ( J:238318 )

• drastic reduction in the frequency and absolute number of TCR beta+ T cells in the mesenteric lymph nodes

• however, the colonic lamina propria contains TCR beta+ T cells

• some mice have up to 10 times more T cells in colonic lamina propria than wild-type mice

increased CD4-positive, alpha-beta T cell number ( J:238318 )

• the majority of TCR alpha beta+ T cells in the mesenteric lymph nodes and colonic lamina propria are CD4+ T cells compared to wild-type mice

• accumulation of CD4+ T cells in the colonic lamina propria

decreased NK T cell number ( J:238318 )

• the TCR beta+NK1.1+ natural killer T cell population in the thymus and liver and alpha-GalCer/CD1d-reacted natural killer T cell population in the liver are hardly detectable in mice

abnormal intraepithelial T cell number ( J:238318 )

• reduction in the frequencies and absolute numbers of TCR beta+ intestinal intraepithelial lymphocytes (IEL) in both the small and large intestine

• both the CD8 alpha-alpha+ and CD8 alpha-beta+ cell populations of TCR beta+ IELs are almost completely absent

• the CD4+CD8 alpha-alpha+ cell population in TCR beta+CD8 beta- cells is decreased in the small and large intestine

• the colon exclusive TCR beta+CD4-CD8 alpha-CD8 beta- cell population is absent

• the remaining TCR beta+ IEL fraction is CD4+ T cells

• thymic IEL precursors (TCR alpha-beta+CD4-CD8-NK1.1-) are decreased in both frequency and absolute number; this reduction is due to almost complete loss of CD103+ cell population coexpressing both CD5 and CD122

increased gamma-delta intraepithelial T cell number ( J:238318 )

• increase in the frequency of TCR gamma-delta+ IELs in the small and large intestines and the absolute numbers of these IELs are increased in the colon but not the small intestine

abnormal regulatory T cell number ( J:238318 )

• frequency of regulatory T cells is higher in mesenteric lymph nodes and lower in colonic lamina propria in mice older than 10 weeks of age, however, absolute numbers of regulatory T cells are unchanged

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:238318 )

• reduction in frequency of CD25+Foxp3+ cells in CD4 single positive thymocytes of 10 week old mice that do not have colitis

abnormal alpha-beta intraepithelial T cell morphology ( J:238318 )

• thymic IEL precursors (TCRalphabeta+CD4-CD8-NK1.1-) stimulated with an agonistic anti-CD3 antibody in vitro do not show enlargement of cell size and induced expression of CD25, IL-2Ralpha chain as seen in wild-type cells

• thymic IEL precursors treated with the agonistic anti-CD3 antibody show inefficient induction of CD8alpha induction

abnormal CD4-positive, alpha-beta T cell physiology ( J:238318 )

• CD4+ T cells from colonic lamina propria and mesenteric lymph nodes stimulated with PMA plus ionomycin exhibit a more robust production of IFN-gamma and IL-17A than in wild-type cells

abnormal regulatory T cell physiology ( J:238318 )

• in an in vitro suppression assay, regulatory T cells show less suppressive activity than wild-type T cells, indicating failure of suppressive function of the leaky regulatory T cells

abnormal cytokine level ( J:238318 )

• colons show increased mRNA levels of proinflammatory cytokines and RegIII-beta/gamma proteins (antimicrobial peptides)

• elevation of expression of IFN-gamma and IL-17