The skeletal phenotype of achondrogenesis type 1A is caused exclusively by cartilage defects

Ian M. Bird, Susie H. Kim, Devin K. Schweppe, Joana Caetano-Lopes, Alexander G. Robling, Julia F. Charles, Steven P. Gygi, Matthew L. Warman, Patrick J. Smits

Research output: Contribution to journalArticle

5 Scopus citations


Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by Trip11) cause achondrogenesis type 1A (ACG1A). ACG1A is surprisingly tissue specific, mainly affecting cartilage development. Bone development is also abnormal, but as chondrogenesis and osteogenesis are closely coupled, this could be a secondary consequence of the cartilage defect. A possible explanation for the tissue specificity of ACG1A is that cartilage and bone are highly secretory tissues with a high use of the membrane trafficking machinery. The perinatal lethality of ACG1A prevents investigating this hypothesis. We therefore generated mice with conditional Trip11 knockout alleles and inactivated Trip11 in chondrocytes, osteoblasts, osteoclasts and pancreas acinar cells, all highly secretory cell types. We discovered that the ACG1A skeletal phenotype is solely due to absence of GMAP-210 in chondrocytes. Mice lacking GMAP-210 in osteoblasts, osteoclasts and acinar cells were normal. When we inactivated Trip11 in primary chondrocyte cultures, GMAP-210 deficiency affected trafficking of a subset of chondrocyte-expressed proteins rather than globally impairing membrane trafficking. Thus, GMAP-210 is essential for trafficking specific cargoes in chondrocytes but is dispensable in other highly secretory cells.

Original languageEnglish (US)
Article numberdev156588
JournalDevelopment (Cambridge)
Issue number1
StatePublished - Jan 2018



  • Achondrogenesis type 1A
  • Cartilage
  • Conditional knockout
  • GMAP-210
  • Golgin
  • Proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Bird, I. M., Kim, S. H., Schweppe, D. K., Caetano-Lopes, J., Robling, A. G., Charles, J. F., Gygi, S. P., Warman, M. L., & Smits, P. J. (2018). The skeletal phenotype of achondrogenesis type 1A is caused exclusively by cartilage defects. Development (Cambridge), 145(1), [dev156588].