Heritable susceptibility for colitis in mice induced by IL-10 deficiency.
Severity of inflammatory bowel disease in IL-10 gene-targeted mice is in part determined by genetic background. In the current study, a targeted IL-10 gene was transferred into the C3H/HeJBir substrain, known to exhibit high T-cell and B-cell responses to enteric flora, and to be highly sensitive to colitigenic stress. IL-10-deficient C3H/HeJBir mice developed early onset colitis in contrast to IL-10-deficient C57BL/6J congenic mice. Histopathologic analysis of disease in C3H/HeJBir.Il10-/- and C57BL/6J.Il10-/- mice showed significant differences at all ages studied. Hybrids of these congenic strains (F1.Il10-/-) were produced to study the mode of inheritance as well as subphenotypes that correlated with histopathology. Lesions in F1 mice were intermediate between parental strains. C3H-contributed subphenotypes that correlated best with histopathology were peripheral blood granulocyte percentage, serum amyloid A concentration, spleen weight/body weight ratio, and mesenteric lymph node weight/ body weight ratio. Neither enhanced humoral immunity (secretory IgA, anti-Escherichia coli cellular membrane Ig) characteristic of C3H/HeJBir, nor T-cell percentages in peripheral blood correlated as well. This study represents a necessary step in elucidating murine genetic modifiers controlling colitis sensitivity.
Bristol
I J
IJ
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Farmer
M A
MA
Cong
Y
Y
Zheng
X X
XX
Strom
T B
TB
Elson
C O
CO
Sundberg
J P
JP
Leiter
E H
EH
D000818:Animals; D000938:Antigen-Presenting Cells; D015496:CD4-Positive T-Lymphocytes; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D016207:Cytokines; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D016207:Cytokines; D016753:Interleukin-10