TY - JOUR
T1 - Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic a cells
AU - Efrat, Shimon
AU - Teitelman, Gladys
AU - Anwar, Muhammad
AU - Ruggiero, David
AU - Hanahan, Douglas
N1 - Funding Information:
We thank Joel Habener for the rat preproglucagon gene, for CLP-I antiserum, and for helpful discussions throughout the course of this study. We also thank Jeff Hager and Joan Alexander for mouse genetic analysis, David lane for Tag antiserum, Jim Duffy for artwork, Dave Greene for photography, Marilyn Goodwin for preparation of the manuscript, and Ron Evans, Robert Edwards, Lorraine lacovitti, and Marian Evinger for comments on the manuscript. S. E. is supported by the Cancer Research Institute/David Jacobs Memorial Fellowship. D. R. is supported by Established Investigatorship and Grant-in-Aid grants from the American Heart Association. This work was funded by grants from Monsanto company and the National Institutes of Health (including HL18974 and DK38171).
PY - 1988/9
Y1 - 1988/9
N2 - The regulatory region of the rat preproglucagon gene targets expression of the SV40 large T oncoprotein to two cell types in transgenic mice, the pancreatic α cells and a set of neurons localized in the hindbrain, both of which normally produce preproglucagon. Additional neurons in the forebrain and midbrain stain for T antigen but do not express the endogenous glucagon gene. Synthesis of T antigen in endocrine α cells results in the heritable development of pancreatic glucagonomas. In brains of transgenic mice from three independent lineages, expression of the hybrid gene begins at embryonic day 12 in neuroblasts of the hindbrain, where it continues throughout adult life, most notably in the medulla. Remarkably, oncoprotein expression in both proliferating neuroblasts and mature neurons has no apparent consequences, either phenotypic or tumorigenic. Expression of the hybrid glucagon gene in both neurons and islet cells supports a possible interrelationship between these cell types.
AB - The regulatory region of the rat preproglucagon gene targets expression of the SV40 large T oncoprotein to two cell types in transgenic mice, the pancreatic α cells and a set of neurons localized in the hindbrain, both of which normally produce preproglucagon. Additional neurons in the forebrain and midbrain stain for T antigen but do not express the endogenous glucagon gene. Synthesis of T antigen in endocrine α cells results in the heritable development of pancreatic glucagonomas. In brains of transgenic mice from three independent lineages, expression of the hybrid gene begins at embryonic day 12 in neuroblasts of the hindbrain, where it continues throughout adult life, most notably in the medulla. Remarkably, oncoprotein expression in both proliferating neuroblasts and mature neurons has no apparent consequences, either phenotypic or tumorigenic. Expression of the hybrid glucagon gene in both neurons and islet cells supports a possible interrelationship between these cell types.
UR - http://www.scopus.com/inward/record.url?scp=0024074541&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(88)90110-9
DO - 10.1016/0896-6273(88)90110-9
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AN - SCOPUS:0024074541
SN - 0896-6273
VL - 1
SP - 605
EP - 613
JO - Neuron
JF - Neuron
IS - 7
ER -