November 12, 2014
Notes: Tu, Yuliang
Asian J Surg. 2013 Oct;36(4):159-64. doi: 10.1016/j.asjsur.2013.04.003. Epub 2013 Jun 17.
Author Address: Department of Hepatobiliary Surgery, First Affiliated Hospital of People’s Liberation Army (PLA) General Hospital, Beijing, China.
Reference Type: Journal Article
Record Number: 5109Author: Ulmasov, B., Oshima, K., Rodriguez, M. G., Cox, R. D. and Neuschwander-Tetri, B. A.
Title: Differences in the degree of cerulein-induced chronic pancreatitis in C57BL/6 mouse substrains lead to new insights in identification of potential risk factors in the development of chronic pancreatitis
Journal: Am J Pathol
Short Title: Differences in the degree of cerulein-induced chronic pancreatitis in C57BL/6 mouse substrains lead to new insights in identification of potential risk factors in the development of chronic pancreatitis
Alternate Journal: The American journal of pathology
ISSN: 1525-2191 (Electronic)
Accession Number: 23845568
Gene Expression Profiling
Gene Expression Regulation
Genetic Association Studies
Mice, Inbred C57BL
Pancreatic Stellate Cells/metabolism/pathology
Pancreatitis, Chronic/*chemically induced/enzymology/*pathology
Abstract: A frequently used experimental model of chronic pancreatitis (CP) recapitulating human disease is repeated injection of cerulein into mice. C57BL/6 is the most commonly used inbred mouse strain for biomedical research, but widespread demand has led to generation of several substrains with subtly different phenotypes. In this study, two common substrains, C57BL/6J and C57BL/6NHsd, exhibited different degrees of CP, with C57BL/6J being more susceptible to repetitive cerulein-induced CP as assessed by pancreatic atrophy, pancreatic morphological changes, and fibrosis. We hypothesized that the deficiency of nicotinamide nucleotide transhydrogenase (NNT) protein in C57BL/6J is responsible for the more severe C57BL/6J phenotype but the parameters of CP in NNT-expressing transgenic mice generated on a C57BL6/J background do not differ with those of wild-type C57BL/6J. The highly similar genetic backgrounds but different CP phenotypes of these two substrains presents a unique opportunity to discover genes important in pathogenesis of CP. We therefore performed whole mouse genome Affymetrix microarray analysis of pancreatic gene expression of C57BL/6J and C57BL/6NHsd before and after induction of CP. Genes with differentially regulated expression between the two substrains that might be candidates in CP progression included Mmp7, Pcolce2, Itih4, Wdfy1, and Vtn. We also identified several genes associated with development of CP in both substrains, including RIKEN cDNA 1810009J06 gene (trypsinogen 5), Ccl8, and Ccl6.