PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Renner, S.* ; Braun-Reichhart, C.* ; Blutke, A.* ; Herbach, N.* ; Emrich, D.* ; Streckel, E.* ; Wünsch, A.* ; Kessler, B.* ; Kurome, M.* ; Bahr, A.* ; Klymiuk, N.* ; Krebs, S.* ; Puk, O. ; Nagashima, H.* ; Graw, J. ; Blum, H.* ; Wanke, R.* ; Wolf, E.*

Permanent neonatal diabetes in INSC94Y transgenic pigs.

Diabetes 62, 1505-1511 (2013)
Publ. Version/Full Text Volltext DOI PMC
Closed
Open Access Green as soon as Postprint is submitted to ZB.
Mutations in the insulin (INS) gene may cause permanent neonatal diabetes mellitus (PNDM). Ins2 mutant mouse models provided important insights into the disease mechanisms of PNDM but have limitations for translational research. To establish a large animal model of PNDM, we generated INSC94Y transgenic pigs. A line expressing high levels of INSC94Y mRNA (70-86% of wildtype INS transcripts) exhibited elevated blood glucose soon after birth but unaltered beta-cell mass at the age of 8 days. At 4.5 months, INSC94Y transgenic pigs exhibited 41% reduced body weight, 72% decreased beta-cell mass (-53% relative to body weight), and 60% lower fasting insulin levels compared with littermate controls. beta-cells of INSC94Y transgenic pigs showed a marked reduction of insulin secretory granules and severe dilation of the endoplasmic reticulum. Cataract development was already visible in 8-day-old INSC94Y transgenic pigs and became more severe with increasing age. Diabetes-associated pathological alterations of kidney and nervous tissue were not detected during the observation period of 1 year. The stable diabetic phenotype and its rescue by insulin treatment make the INSC94Y transgenic pig an attractive model for insulin supplementation and islet transplantation trials, and for studying developmental consequences of maternal diabetes mellitus.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
7.895
2.093
66
76
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Endoplasmic-reticulum ; Human Insulin ; Mutant Mice ; Beta-cells ; Mutations ; Mellitus ; Stress ; Growth ; Model
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 62, Issue: 5, Pages: 1505-1511 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500500-002
PubMed ID 23274907
DOI 10.2337/db12-1065
WOS ID WOS:000318128700029
Scopus ID 84876517346
Erfassungsdatum 2013-05-31
[➜Report correction]