Reference SummaryMahler M, Am J Physiol 1998 Mar;274(3 Pt 1):G544-51

Title

 Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis.

Authors

 Mahler M; Bristol IJ; Leiter EH; Workman AE; Birkenmeier EH; Elson CO; Sundberg JP

Journal

 Am J Physiol

Volume

 274

Issue

 3 Pt 1

Year

 1998

Pages

 G544-51

Abstract

 Dextran sulfate sodium (DSS)-induced murine colitis represents an experimental model for human inflammatory bowel disease. The aim of this study was to screen various inbred strains of mice for genetically determined differences in susceptibility to DSS-induced colitis. Mice of strains C3H/HeJ, C3H/HeJBir, C57BL/6J, DBA/2J, NOD/LtJ, NOD/LtSz-Prkdc(scid)/Prkdc(scid), 129/ SvPas, NON/LtJ, and NON.NOD-H2g7 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, ulceration, hyperplasia, and area involved. Image analysis was used to quantitate the proportion of cecum ulcerated. Histological examination revealed significant differences among inbred strains for all parameters scored. In both cecum and colon, C3H/HeJ and a recently selected substrain, C3H/ HeJBir, were highly DSS susceptible. NOD/LtJ, an autoimmune-prone strain, and NOD/LtSz-Prkdc(scid)/Prkdc(scid), a stock with multiple defects in innate and adoptive immunity, were also highly DSS susceptible. NON/LtJ, a strain closely related to NOD, was quite DSS resistant. The major histocompatibility (MHC) haplotype of NOD mice (H2g7), a major component of the NOD autoimmune susceptibility, was not crucial in determining DSS susceptibility, since NON mice congenic for this MHC haplotype retained resistance. C57BL/6J, 129/SvPas, and DBA/2J mice showed various degrees of susceptibility, depending upon the anatomical site. A greater male susceptibility to DSS-induced colonic but not cecal lesions was observed. In summary, this study demonstrates major differences in genetic susceptibility to DSS-induced colitis among inbred strains of mice. Knowledge of these strain differences in genetic responsiveness to acute inflammatory stress in the large intestine will permit design of genetic crosses to elucidate the genes involved.

Links

 J:46553 – MGI References
9530156 – National Library of Medicine/PubMed

Strain Notes

Strain Note
129S2/SvPas These mice were from the Jackson Laboratory.
C3H/HeJ These mice were from the Jackson Laboratory.
C3H/HeJBir These mice were from the Jackson Laboratory.
C57BL/6J These mice were from the Jackson Laboratory.
DBA/2J These mice were from the Jackson Laboratory.
NOD.CB17-Prkdcscid These mice were from Dr. Ed Leiter's colony at The Jackson Laboratory.
NOD/ShiLtJ These mice were from the Jackson Laboratory.
NON/ShiLtJ These mice were from the Jackson Laboratory.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C3H/HeJBir Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
C3H/HeJ Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
NOD.CB17-Prkdcscid Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
NOD/ShiLtJ Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
DBA/2J Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
C57BL/6J Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
NON.NOD-H2g7 Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
NON/ShiLtJ Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
129S2/SvPas Intestine - Large Intestine - Cecum hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Cecum

observed
C3H/HeJBir Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
NOD/ShiLtJ Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
C3H/HeJ Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
C57BL/6J Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
NOD.CB17-Prkdcscid Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
129S2/SvPas Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
NON.NOD-H2g7 Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
NON/ShiLtJ Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
DBA/2J Intestine - Large Intestine - Colon hyperplasia
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed