Human Molecular Genetics Advance Access published online on May 5, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh150
© 2004 by Oxford University Press
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1 Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: nelson{at}bcm.tmc.edu.
FXR1 is one of the two known homologues of FMR1. FXR1 shares a high degree of sequence homology with FMR1 and also encodes two KH domains and a RGG domain conferring RNA binding capabilities. In comparison to FMRP, very little is known regarding the function of FXR1P in vivo. Mouse knockout models exist for both Fmr1 and Fxr2. To study the function of Fxr1 in vivo, we generated an Fxr1 knockout mouse model. Homozygous Fxr1 knockout neonates die shortly after birth most likely due to cardiac or respiratory failure. Histochemical analyses carried out on both skeletal and cardiac muscles show a disruption of cellular architecture and structure in E19 Fxr1 neonates compared to wild type littermates. In wild type E19 skeletal and cardiac muscle, Fxr1p is localized to the costameric regions within the muscles. In E19 Fxr1 knockout littermates, in addition to the absence of Fxr1p, costameric proteins vinculin, dystrophin and
Article
Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo
2 Department of Molecular and Human Genetics Baylor, College of Medicine, Houston, TX, USA; Present address: Lexicon Genetics, The Woodlands, TX, USA
3 Department of Pathology, Erasmus University, Rotterdam, The Netherlands
4 Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch Cedex, France
5 Department of Molecular and Human Genetics Baylor, College of Medicine, Houston, TX, USA
Abstract 
-actinin were found to be delocalised. A second mouse model (Fxr1+neo), which expresses strongly reduced levels of Fxr1p relative to wild type littermates, does not display the neonatal lethal phenotype seen in the Fxr1 knockouts but does display a strongly reduced limb musculature and has a reduced life span of about 18 weeks. The results presented here point towards a role for Fxr1p in muscle mRNA transport/translation control similar to that seen for Fmrp in neuronal cells.
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