title: Mice with a conditional deletion of the neurotrophin receptor TrkB are dwarfed, and are similar to mice with a MAPK14 deletion.
abstract: Long bone growth results from ordered chondrocyte development within the cartilagenous growth plate. Chondrocytes are recruited from a resting pool to proliferate along the long axis of the bone, until various signals trigger differentiation and hypertrophy. We have shown previously that the neurotrophin receptor TrkB is expressed in growth plate chondrocytes, where the tyrosine kinase receptor regulates the pace of hypertrophic differentiation by modulating the activities of ERK and p38 MAP kinases. To investigate the physiological relevance of TrkB to bone growth in vivo, we generated mice with a targeted disruption of the receptor, and compared them to mice targeted for MAPK14, the gene for p38α. The TrkB mutant and p38α mutant mice showed a similar degree of dwarfism and delayed hypertrophic differentiation. To extend these findings, we showed that both the TrkB and p38α mutant mice have altered expression of Runx2 and Sox9, two key transcription factors required for skeletogenesis. The data provides in vivo evidence for the role of TrkB in bone growth, supports the role of p38 downstream of TrkB, and suggests that Runx2 and Sox9 expression is regulated by this pathway at the growth plate.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America. Michele.hutchison@utsw.edu
authors.forename: Michele R
authors.initials: MR
authors.lastname: Hutchison
mesh_terms: D000818:Animals; D019902:Chondrocytes / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004392:Dwarfism / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics*; D009154:Mutation; D020813:Receptor, trkB / Q000235:genetics*; D055758:SOX9 Transcription Factor / Q000235:genetics; D015398:Signal Transduction
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D020813:Receptor, trkB; D048308:Mitogen-Activated Protein Kinase 14