Leukemia inhibitory factor induces neurotransmitter switching in transgenic mice.
Leukemia inhibitory factor (LIF) is a cytokine growth factor that induces rat sympathetic neurons to switch their neurotransmitter phenotype from noradrenergic to cholinergic in vitro. To test whether LIF can influence neuronal differentiation in vivo, we generated transgenic mice that expressed LIF in pancreatic islets under the control of the insulin promoter and evaluated the neurotransmitter phenotype of the pancreatic sympathetic innervation. We also used the insulin promoter to coexpress nerve growth factor in the islets, which greatly increased the density of sympathetic innervation and facilitated analysis of the effects of LIF. Our data demonstrate that tyrosine hydroxylase and catecholamines declined and choline acetyltransferase increased in response to LIF. We conclude that LIF can induce neurotransmitter switching of sympathetic neurons in vivo.
Bamber
B A
BA
Department of Biochemistry, University of Washington, Seattle 98195.
Masters
B A
BA
Hoyle
G W
GW
Brinster
R L
RL
Palmiter
R D
RD
D000375:Aging / Q000502:physiology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002454:Cell Differentiation; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003433:Crosses, Genetic; D005260:Female; D015870:Gene Expression; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics; D015850:Interleukin-6; D007515:Islets of Langerhans / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology*; D010179:Pancreas / Q000166:cytology / Q000294:innervation*; D011401:Promoter Regions, Genetic; D013564:Sympathetic Nervous System / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002395:Catecholamines; D006131:Growth Inhibitors; D007328:Insulin; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase