Full name (if applicable):
Targeted replacement of the Mist1 gene with LacZ. The LacZ gene is inserted 8 bp upstream of the translational start site leading to complete recapitulation of Mist1 expression by LacZ. The enture coding region was replaced.
Mist1-/- mice are viable and fertile with no obvious reprductive phenotypes. All serous exocrine cells currently examined witin these mice exhibit diruptions in organization and gene expression. In particular, pancreatic acinar cell organization is disrupted, there is premature activation of digestive enzymes and an increase in cell proliferation. The genes that are known to show decrease expression in these mice include Cx32 (Gjb1), Rab3D, SPCA2 (Atp2c2), P21 and IP3R3. Genes that show increased expression include CCK AR, PAP1 and Reg1.
Mist1-/- mice are more senstive to cerulein-induced pancreatitis, and have a decreased ability to activate the ER stress response upon injury. These mice also exhibit increased acinar to duct cell metaplasia.
Targeted knockout through homologous recombination in ES cells
Number of backcrossed generations:
1: Jia D, Sun Y, Konieczny SF. Mist1 regulates pancreatic acinar cell proliferation through p21 CIP1/WAF1. Gastroenterology. 2008 Nov;135(5):1687-97. 2: Kowalik AS, Johnson CL, Chadi SA, Weston JY, Fazio EN, Pin CL. Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1123-32. 3: Fazio EN, Pin CL. Mist1-null mice are resistant to streptozotocin-induced beta cell damage. Biochem Biophys Res Commun. 2007 Feb 16;353(3):823-8. 4: Ramsey VG, Doherty JM, Chen CC, Stappenbeck TS, Konieczny SF, Mills JC. The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1. Development. 2007 Jan;134(1):211-22. 5: Zhao Y, Johansson C, Tran T, Bettencourt R, Itahana Y, Desprez PY, Konieczny SF. Identification of a basic helix-loop-helix transcription factor expressed in mammary gland alveolar cells and required for maintenance of the differentiated state. Mol Endocrinol. 2006 Sep;20(9):2187-98. 6: Fazio EN, Everest M, Colman R, Wang R, Pin CL. Altered Glut-2 accumulation and beta-cell function in mice lacking the exocrine-specific transcription factor, Mist1. J Endocrinol. 2005 Dec;187(3):407-18. 7: Luo X, Shin DM, Wang X, Konieczny SF, Muallem S. Aberrant localization of intracellular organelles, Ca2+ signaling, and exocytosis in Mist1 null mice. J Biol Chem. 2005 Apr 1;280(13):12668-75. 8: Johnson CL, Kowalik AS, Rajakumar N, Pin CL. Mist1 is necessary for the establishment of granule organization in serous exocrine cells of the gastrointestinal tract. Mech Dev. 2004 Mar;121(3):261-72. 9: Rukstalis JM, Kowalik A, Zhu L, Lidington D, Pin CL, Konieczny SF. Exocrine specific expression of Connexin32 is dependent on the basic helix-loop-helix transcription factor Mist1. J Cell Sci. 2003 Aug 15;116(Pt 16):3315-25. 10: Pin CL, Rukstalis JM, Johnson C, Konieczny SF. The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity. J Cell Biol. 2001 Nov 12;155(4):519-30.