PMID- 10049364
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 4
DP  - 1999 Feb 15
TI  - Inactivation of the winged helix transcription factor HNF3alpha affects glucose
      homeostasis and islet glucagon gene expression in vivo.
PG  - 495-504
AB  - Mice homozygous for a null mutation in the winged helix transcription factor
      HNF3alpha showed severe postnatal growth retardation followed by death between P2
      and P12. Homozygous mutant mice were hypoglycemic despite unchanged expression of
      HNF3 target genes involved in hepatic gluconeogenesis. Whereas insulin and
      corticosteroid levels were altered as expected, plasma glucagon was reduced
      markedly in the mutant animals despite the hypoglycemia that should be expected
      to increase glucagon levels. This correlated with a 70% reduction in pancreatic
      proglucagon gene expression. We also showed that HNF3alpha could bind to and
      transactivate the proglucagon gene promoter. These observations invoke a central 
      role for HNF3alpha in the regulatory control of islet genes essential for glucose
      homeostasis in vivo.
FAU - Kaestner, K H
AU  - Kaestner KH
AD  - Department of Genetics, University of Pennsylvania School of Medicine,
      Philadelphia, Pennsylvania 19104-6145, USA. kaestner@mail.med.upenn.edu
FAU - Katz, J
AU  - Katz J
FAU - Liu, Y
AU  - Liu Y
FAU - Drucker, D J
AU  - Drucker DJ
FAU - Schutz, G
AU  - Schutz G
LA  - eng
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - R01 DK055342/DK/NIDDK NIH HHS/United States
GR  - P30 DK50306/DK/NIDDK NIH HHS/United States
GR  - P30 DK019525/DK/NIDDK NIH HHS/United States
GR  - P30 DK19525/DK/NIDDK NIH HHS/United States
GR  - R01 DK55342-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxa1 protein, mouse)
RN  - 0 (Foxf2 protein, mouse)
RN  - 0 (Glucocorticoids)
RN  - 0 (Hepatocyte Nuclear Factor 3-alpha)
RN  - 0 (Insulin)
RN  - 0 (LUN protein, vertebrate)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 55963-74-1 (Proglucagon)
RN  - 9007-92-5 (Glucagon)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Body Weight/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Forkhead Transcription Factors
MH  - Gene Expression Regulation/genetics
MH  - Gene Targeting
MH  - Genes, Reporter/genetics
MH  - Glucagon/blood/*genetics
MH  - Glucocorticoids/blood
MH  - Gluconeogenesis/genetics
MH  - Glucose/*metabolism
MH  - Hepatocyte Nuclear Factor 3-alpha
MH  - Histocytochemistry
MH  - Homeostasis/physiology
MH  - Hypoglycemia/genetics
MH  - Insulin/blood
MH  - Islets of Langerhans/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Nuclear Proteins/*genetics
MH  - Proglucagon
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Precursors/genetics
MH  - RNA, Messenger/metabolism
MH  - Trans-Activators/*genetics
MH  - Transcription Factors/*genetics
MH  - Transcriptional Activation/genetics
PMC - PMC316473
EDAT- 1999/02/27 00:00
MHDA- 1999/02/27 00:01
CRDT- 1999/02/27 00:00
PHST- 1999/02/27 00:00 [pubmed]
PHST- 1999/02/27 00:01 [medline]
PHST- 1999/02/27 00:00 [entrez]
AID - 10.1101/gad.13.4.495 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Feb 15;13(4):495-504. doi: 10.1101/gad.13.4.495.