title: Diabetes Caused by Elastase-Cre-Mediated Pdx1 Inactivation in Mice.
abstract: Endocrine and exocrine pancreas tissues are both derived from the posterior foregut endoderm, however, the interdependence of these two cell types during their formation is not well understood. In this study, we generated mutant mice, in which the exocrine tissue is hypoplastic, in order to reveal a possible requirement for exocrine pancreas tissue in endocrine development and/or function. Since previous studies showed an indispensable role for Pdx1 in pancreas organogenesis, we used Elastase-Cre-mediated recombination to inactivate Pdx1 in the pancreatic exocrine lineage during embryonic stages. Along with exocrine defects, including impaired acinar cell maturation, the mutant mice exhibited substantial endocrine defects, including disturbed tip/trunk patterning of the developing ductal structure, a reduced number of Ngn3-expressing endocrine precursors, and ultimately fewer β cells. Notably, postnatal expansion of the endocrine cell content was extremely poor, and the mutant mice exhibited impaired glucose homeostasis. These findings suggest the existence of an unknown but essential factor(s) in the adjacent exocrine tissue that regulates proper formation of endocrine precursors and the expansion and function of endocrine tissues during embryonic and postnatal stages.
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Sota
authors.initials: S
authors.lastname: Kodama
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Furuyama
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuhara
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Masui
authors.forename: Michiya
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Vanderbilt Developmental Biology Program, Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Gannon
authors.affiliation: Vanderbilt Developmental Biology Program, Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D019426:Integrases; D051379:Mice; D018345:Mice, Knockout; D046790:Pancreas, Exocrine / Q000196:embryology / Q000378:metabolism*; D010196:Pancreatic Elastase; D015534:Trans-Activators / Q000172:deficiency*
chemical_list: D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C045073:Cre recombinase; D019426:Integrases; D010196:Pancreatic Elastase