title: Phenotypic characterization of miR-92a-/- mice reveals an important function of miR-92a in skeletal development.
abstract: MicroRNAs (miRNAs, miRs) emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17∼92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17∼92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17∼92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a-/- mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a-/- mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a-/- mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.
authors: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, J. W. Goethe University Frankfurt, Frankfurt am Main, Germany.
authors: Daniela
authors: D
authors: Penzkofer
authors: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, J. W. Goethe University Frankfurt, Frankfurt am Main, Germany.
authors: Angelika
authors: A
authors: Bonauer
authors: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, J. W. Goethe University Frankfurt, Frankfurt am Main, Germany.
authors: Ariane
authors: A
authors: Fischer
authors: Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Marburg, Germany.
authors: Alexander
authors: A
authors: Tups
authors: Institute for Cardiovascular Physiology, J. W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Centre of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany.
authors: Ralf P
authors: RP
authors: Brandes
authors: Department of Cardiology, Internal Medicine III, J. W. Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; German Centre of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany.
authors: Andreas M
authors: AM
authors: Zeiher
authors: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, J. W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Centre of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany.
authors: Stefanie
authors: S
authors: Dimmeler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D001846:Bone Development / Q000235:genetics*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype
chemical_list: D035683:MicroRNAs; C541873:Mirn92 microRNA, mouse