TAILIEUCHUNG - Báo cáo khoa học: Mice with a targeted disruption of the Fgfrl1 gene die at birth due to alterations in the diaphragm

FGFRL1 is a recently discovered member of the fibroblast growth factor receptor family that is lacking the intracellular tyrosine kinase domain. To elucidate the function of the novel receptor, we created mice with a tar-geted disruption of the Fgfrl1gene. | ỊFEBS Journal Mice with a targeted disruption of the Fgfrll gene die at birth due to alterations in the diaphragm Stefan Baertschi1 Lei Zhuang1 and Beat Trueb1 2 1 ITI Research Institute University of Bern Switzerland 2 Department of Rheumatology and ClinicalImmunology Allergology University Hospital Bern Switzerland Keywords diaphragm fibroblast growth factor FGF fibroblast growth factor receptor FGFR knockout mice muscle development Correspondence B. Trueb ITI Research Institute PO Box 54 CH-3010 Bern Switzerland Fax 41 632 4963 Tel 41 632 8726 E-mail Received 14 August 2007 revised 10 October 2007 accepted 15 October 2007 doi FGFRL1 is a recently discovered member of the fibroblast growth factor receptor family that is lacking the intracellular tyrosine kinase domain. To elucidate the function of the novel receptor we created mice with a targeted disruption of the Fgfrll gene. These mice develop normally until term but die within a few minutes after birth due to respiratory failure. The respiratory problems are explained by a significant reduction in the size of the diaphragm muscle which is not sufficient to inflate the lungs after birth. The remaining portion of the diaphragm muscle appears to be well developed and innervated. It consists of differentiated myofibers with nuclei at the periphery. Fast and slow muscle fibers occur in normal proportions. The myogenic regulatory factors MyoD Myf5 myogenin and Mrf4 and the myocyte enhancer factors Mef2A Mef2B Mef2C and Mef2D are expressed at normal levels. Experiments with a cell culture model involving C2C12 myoblasts show that Fgfrll is expressed during the late stages of myotube formation. Other skeletal muscles do not appear to be affected in the Fgfrll deficient mice. Thus Fgfrll plays a critical role in the development of the diaphragm. The fibroblast growth factors FGFs and their receptors play an important role during mammalian development. Human .

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