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J. Biol. Chem., Vol. 275, Issue 49, 38693-38698, December 8, 2000
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From the Department of Paediatrics, The University of Hong Kong,
Queen Mary Hospital, Hong Kong, China
The epidermal growth factor (EGF) family of
peptides signals through the erbB family of receptor tyrosine kinases
and plays important roles in development and tumorigenesis. Both EGF
and transforming growth factor (TGF)-
Expression of Epidermal Growth Factor in Transgenic Mice
Causes Growth Retardation*
§ and¶
only bind to erbB1 and
activate it. The precursor of EGF is distinct from that of TGF- in
having eight additional EGF-like repeats. We have recently shown that the EGF precursor without these repeats is biologically active and
leads to hypospermatogenesis in transgenic mice. Here we present evidence that the growth of transgenic mice widely expressing this
engineered EGF precursor is also stunted. These mice were consistently
born at half the normal weight and reached almost 80% of normal weight
at adulthood. The mechanism involved a reduction of serum insulin-like
growth factor-binding protein-3. Chondrocyte development in the growth
plate was affected, and osteoblasts accumulated in the endosteum and
periosteum. Besides these novel findings on the in vivo
effects of EGF on bone development, we observed no sign of tumor
formation in our transgenic animals. In contrast to previous reports on
TGF- transgenic mice, we show that the biological functions of EGF
and TGF- are clearly distinct.
*
This work was supported by a grant from the Hong Kong
Research Grants Council (to S.-Y. C.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The contribution of these two authors was equal.
§
To whom correspondence should be addressed. Tel.: 852-28554634;
Fax: 852-28551523; E-mail: sychan@hkucc.hku.hk.
¶
Recipient of the Lee Po Chun Overseas Scholar Award (2000).
Present address: Department of Anatomy and Cell Biology,
Graduate School of Medicine, University of Tokyo, Tokyo
113-0033, Japan.
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