Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic a cells

Shimon Efrat, Gladys Teitelman, Muhammad Anwar, David Ruggiero, Douglas Hanahan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)605-613
Number of pages9
JournalNeuron
Volume1
Issue number7
DOIs
StatePublished - Sep 1988
Externally publishedYes

Fingerprint

Dive into the research topics of 'Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic a cells'. Together they form a unique fingerprint.

Cite this