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The C-terminal cytoplasmic domain of human proEGF is a negative modulator of body and organ weights in transgenic mice
Authors:Thomas Klonisch  Aleksandra Glogowska  Ana A Gratao  Andreea Nistor  Ekkehard Weber  Birgit Rathkolb  Cuong Hoang-Vu  Marlon R Schneider
Institution:a Department of Human Anatomy and Cell Science, University of Manitoba, 130-745 Bannatyne Avenue, Winnipeg, Canada R3E0J9
b Department of Medical Microbiology and Infectious Diseases, University of Manitoba, 130-745 Bannatyne Avenue, Winnipeg, Canada R3E0J9
c Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany
d Department of Surgery, University of Manitoba, GF547-820 Sherbrook Street, Winnipeg, Canada R3A 1R9
e Institute of Physiological Chemistry, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany
f Institute of Experimental Genetics, Helmholtz Center Munich, Oberschleissheim, Germany
g German Mouse Clinic, Helmholtz Center Munich, Oberschleissheim, Germany
h Clinics of Surgery, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany
Abstract:We generated transgenic mice to study the in vivo role of the cytoplasmic domain of human proEGF (proEGFcyt). Post-pubertal proEGFcyt transgenic (tg) mice displayed an up to 15% reduction in body weight, including smaller kidney and brain weights as compared to control littermates. Renal histology, gene expression profiles, and functional parameters were normal. In both sexes, serum levels of IGFBP-3 were reduced. Circulating IGF-I/IGF-II levels were unchanged. Histomorphological analysis revealed isolated foci of liver necrosis specific to proEGFcyt tg mice. In conclusion, we identified proEGF cytoplasmic domain as a novel modulator of whole body and organ-specific growth in mice.
Keywords:proEGF cytoplasmic domain  Kidney  Transgenic  Growth  IGFBP-3
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