DIFFERENTIAL SUSCEPTIBILITY OF INBRED MOUSE STRAINS TO DEXTRAN SULFATE SODIUM-INDUCED COLITIS

Dextran sulfate sodium (DSS)-induced murine colitis represents an expe rimental model for human inflammatory bowel disease. The aim of this s tudy was to screen various inbred strains of mice for genetically dete rmined differences in susceptibility to DSS-induced colitis. Mice of s trains C3H/HeJ, C3H/HeJBir, C57BL/6J, DBA/2J, NOD/LtJ, NOD/LtSz-Prkdc( scid)/Prkdc(scid), 129/SvPas, NON/LtJ, and NON.NOD-H2(g7) were fed 3.5 % DSS in drinking water for 5 days and necropsied 16 days later. Ceca and colons were scored for histological lesions based on severity, ulc eration, hyperplasia, and area involved. Image analysis was used to qu antitate the proportion of cecum ulcerated. Histological examination r evealed significant differences among inbred strains for all parameter s scored. In both cecum and colon, C3H/HeJ and a recently selected sub strain, C3H/HeJBir, were highly DSS susceptible. NOD/LtJ, an autoimmun e-prone strain, and NOD/LtSz-Prkdc(scid)/Prkdc(scid), a stock with mul tiple defects in innate and adoptive immunity, were also highly DSS su sceptible. NON/LtJ, a strain closely related to NOD, was quite DSS res istant;The major histocompatibility (MHC) haplotype of NOD mice (H2(g7 )), a major component of the NOD autoimmune susceptibility, was not cr ucial in determining DSS susceptibility, since NON mice congenic for t his MHC haplotype retained resistance. C57BL/6J, 129/SvPas, and DBA/2J mice showed various degrees of susceptibility, depending upon the ana tomical site. A greater male susceptibility to DSS-induced colonic but not cecal lesions was observed. In summary, this study demonstrates m ajor differences in genetic susceptibility to DSS-induced colitis amon g inbred strains of mice. Knowledge of these strain differences in gen etic responsiveness to acute inflammatory stress in the large intestin e will permit design of genetic crosses to elucidate the genes involve d.