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

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- Prkdcscid/Prkdcscid , 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- Prkdcscid/Prkdcscid , 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.

The zinc sensing receptor, ZnR/GPR39, triggers metabotropic calcium signalling in colonocytes and regulates occludin recovery in experimental colitis

“…The control group received water without DSS during the whole experiment. The experimental protocol used in the current project was calibrated for this strain of mice [24]. Since high mortality rates in both genotypes were monitored using the standard protocol [25], we used 2.5% DSS for 6 days only.…”

Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

“…While oral CD8 ϩ T cell tolerance to OVA was induced in pIgR Ϫ/Ϫ mice in this study, the propensity of these mice to abrogate a previously established tolerance was not investigated. It would be interesting to determine whether a state of nontolerance could be more readily induced in pIgR Ϫ/Ϫ mice, such as that observed following dextran sulfate administration to mice (45).…”

Dysfunction in ABCB1A Has Only a Weak Effect on Susceptibility to Dextran Sulfate Sodium-Induced Colitis in SAM Strains

“…Meanwhile, susceptibility to DSS colitis varies among other inbred mouse strains [8], and this strain difference is determined by multiple uncharacterized genes or genetic background [9]. It is not known, however, if difference in genetic background still exerts a major effect on DSS colitis in combination with ABCB1A dysfunction.…”

“…Tissues were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Microscopic evidence of inflammation and disease severity was assessed using a scoring system described previously [8]. Four main grading criteria (depth of inflammatory cell accumulation, ulceration, hyperplasia, and area involved), with four different subgrades of severity (0-3) for each, were used.…”

“…Rather, the difference among SAM strains in susceptibility to DSS colitis appears to be largely determined by differences in genetic backgrounds other than the Abcb1a gene. Indeed, inbred strains of mice show major differences in genetic susceptibility to DSS-induced colitis [8,11]. This differential colitis susceptibility was genetically studied by utilizing a (C3he/heJ × C57BL/6J)F 2 progeny [9].…”