PuSH - Publication Server of Helmholtz Zentrum München

Schneider, M.R.* ; Dahlhoff, M.* ; Herbach, N.* ; Renner-Mueller, I.* ; Dalke, C. ; Puk, O.* ; Graw, J. ; Wanke, R.* ; Wolf, E.*

Betacellulin overexpression in transgenic mice causes disproportionate growth, pulmonary hemorrhage syndrome and complex eye pathology.

Endocrinology 146, 5237-5246 (2005)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
The EGF family comprises a network of ligands and receptors that regulate proper development and elicit diverse functions in physiology and pathology. Betacellulin (BTC) is a rather poorly characterized member of the EGF family whose in vivo effects have been linked mainly to endocrine pancreas, intestine, and mammary gland function. In vitro studies revealed that this growth factor is a potent mitogen for diverse cell types and suggested unique receptor-binding properties. Genetic ablation of BTC in mice yielded a mild phenotype, probably because of opportunistic compensation by other EGF receptor ligands. To study the biological capabilities of BTC in vivo, we generated transgenic mice overexpressing BTC ubiquitously, with highest expression levels in heart, lung, brain, and pancreas. Mice overexpressing BTC exhibit high early postnatal mortality, reduced body weight gain, and impaired longitudinal growth. In addition, a variety of pathological alterations were observed. Cataract and abnormally shaped retinal layers as well as bone alterations leading to a dome-shaped, round head form were hallmarks of BTC transgenic mice. The most important finding and the cause of reduced life expectancy of BTC transgenic mice were severe alterations of the lung. Pulmonary pathology was primarily characterized by alveolar hemorrhage, thickening of the alveolar septa, intraalveolar accumulation of hemosiderin-containing macrophages, and nodular pulmonary remodeling. Thus, our model uncovers multiple consequences of BTC overexpression in vivo. These transgenic mice provide a useful model for examining the effects of BTC excess on different organs.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0013-7227
e-ISSN 1945-7170
Journal Endocrinology
Quellenangaben Volume: 146, Issue: 12, Pages: 5237-5246 Article Number: , Supplement: ,
Publisher Endocrine Society
Publishing Place Chevy Chase, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)