HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Identification of novel SHOX target genes in the developing limb using a transgenic mouse model.

Abstract
Deficiency of the human short stature homeobox-containing gene (SHOX) has been identified in several disorders characterized by reduced height and skeletal anomalies such as Turner syndrome, Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia as well as isolated short stature. SHOX acts as a transcription factor during limb development and is expressed in chondrocytes of the growth plates. Although highly conserved in vertebrates, rodents lack a SHOX orthologue. This offers the unique opportunity to analyze the effects of human SHOX expression in transgenic mice. We have generated a mouse expressing the human SHOXa cDNA under the control of a murine Col2a1 promoter and enhancer (Tg(Col2a1-SHOX)). SHOX and marker gene expression as well as skeletal phenotypes were characterized in two transgenic lines. No significant skeletal anomalies were found in transgenic compared to wildtype mice. Quantitative and in situ hybridization analyses revealed that Tg(Col2a1-SHOX), however, affected extracellular matrix gene expression during early limb development, suggesting a role for SHOX in growth plate assembly and extracellular matrix composition during long bone development. For instance, we could show that the connective tissue growth factor gene Ctgf, a gene involved in chondrogenic and angiogenic differentiation, is transcriptionally regulated by SHOX in transgenic mice. This finding was confirmed in human NHDF and U2OS cells and chicken micromass culture, demonstrating the value of the SHOX-transgenic mouse for the characterization of SHOX-dependent genes and pathways in early limb development.
AuthorsKatja U Beiser, Anne Glaser, Kerstin Kleinschmidt, Isabell Scholl, Ralph Röth, Li Li, Norbert Gretz, Gunhild Mechtersheimer, Marcel Karperien, Antonio Marchini, Wiltrud Richter, Gudrun A Rappold
JournalPloS one (PLoS One) Vol. 9 Issue 6 Pg. e98543 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24887312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Complementary
Topics
  • Animals
  • DNA, Complementary
  • Electrophoretic Mobility Shift Assay
  • Extremities (embryology)
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • In Situ Hybridization
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Real-Time Polymerase Chain Reaction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: