Effects of Bach2 on pancreatic gene expression in mice

The role of Bach2, a transcriptional repressor and key regulator of adaptive immunity, in the pathogenesis of autoimmune pancreatitis (AIP) is incompletely understood. Here, we used C57BL/6N mice with a targeted deletion of the Bach2 gene (Bach2 knockout mice) to study their susceptibility to AIP. The mice were kept for 18 weeks, before the pancreas and further organs were assessed histopathologically and by molecular methods. Results: Consistent with previous studies, Bach2 knockout mice showed reduced growth and developed a fatal lung disease necessitating humane euthanasia at the age of 18 weeks. Pancreatic infiltrates with lymphocytes frequently occurred in Bach2 knockout mice but not in wild-type animals. In more severe cases, this was associated with the focal destruction of exocrine pancreatic tissue and mild fibrosis. In the principal component analysis of pancreatic RNA-seq data, Bach2 knockout mice clustered separately from wild-type comtrols. Further data analysis revealed the activation of processes linked to adaptive immunity in pancreatic tissue of Bach2 knockout mice. We conclude that Bach2-deficient C57BL/6N mice are prone to the spontaneous development of AIP. This could be due to a disturbed immune homeostasis with dysregulated B and T cell activation. We thank Helmholtz Zentrum Muenchen - German Research Center for Environmental Health (GmbH) for providing the mutant mouse line (Allele: Bach2tm1b(EUCOMM)Wtsi), INFRAFRONTIER/EMMA (www.infrafrontier.eu, PMID: 25414328), and EMMA node at Helmholtz Zentrum Muenchen - German Research Center for Environmental Health (GmbH) from which the mouse line was distributed (RRID:IMSR_EM:09104). Associated primary phenotypic information may be found at www.mousephenotype.org. Overall design: Mice with a constitutive whole-body knockout of the Bach2 gene and wild-type controls were kept until they reached 18 weeks of age. RNA was isolated from pancreatic tissue of 2 males and 2 females per group and subjected to RNA seq analysis.