CANT1 deficiency in a mouse model of Desbuquois dysplasia impairs glycosaminoglycan synthesis and chondrocyte differentiation in growth plate cartilage

FEBS Open Bio. 2020 Jun;10(6):1096-1103. doi: 10.1002/2211-5463.12859. Epub 2020 Apr 23.


Desbuquois dysplasia (DD) type 1 is a rare skeletal dysplasia characterized by a short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium-activated nucleotidase 1 (CANT1), which encodes a nucleotidase that preferentially hydrolyzes UDP to UMP and phosphate. In this study, we generated Cant1 KO mice using CRISPR/Cas9-mediated genome editing. All F0 mice possessing frameshift deletions at both Cant1 alleles exhibited a dwarf phenotype. Germline transmission of the edited allele was confirmed in an F0 heterozygous mouse, and KO mice were generated by crossing of the heterozygous breeding pairs. Cant1 KO mice exhibited skeletal defects, including short stature, thoracic kyphosis, and delta phalanx, all of which are observed in DD type 1 patients. The glycosaminoglycan (GAG) content and extracellular matrix space were reduced in the growth plate cartilage of mutants, and proliferating chondrocytes lost their typical flat shape and became round. Chondrocyte differentiation, especially terminal differentiation to hypertrophic chondrocytes, was impaired in Cant1 KO mice. These findings indicate that CANT1 is involved in the synthesis of GAG and regulation of chondrocyte differentiation in the cartilage and contribute to a better understanding of the pathogenesis of DD type 1.

Keywords: CANT1; Desbuquois dysplasia; chondrocyte; extracellular matrix; genome editing; glycosaminoglycan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / deficiency*
  • Acid Anhydride Hydrolases / genetics
  • Animals
  • Cell Differentiation / genetics
  • Chondrocytes / pathology
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Disease Models, Animal
  • Dwarfism / diagnosis
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Female
  • Glycosaminoglycans / biosynthesis
  • Growth Plate / cytology
  • Growth Plate / growth & development
  • Growth Plate / pathology*
  • Humans
  • Joint Instability / diagnosis
  • Joint Instability / genetics*
  • Joint Instability / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Ossification, Heterotopic / diagnosis
  • Ossification, Heterotopic / genetics*
  • Ossification, Heterotopic / pathology
  • Polydactyly / diagnosis
  • Polydactyly / genetics*
  • Polydactyly / pathology
  • Skeleton / diagnostic imaging
  • Skeleton / growth & development


  • Glycosaminoglycans
  • Acid Anhydride Hydrolases
  • Cant1 protein, mouse

Supplementary concepts

  • Desbuquois syndrome