Article Dans Une Revue BONE Année : 2000

The Gene Encoding the Mouse Homologue of the Human Osteoclast-Specific 116-kDa V-ATPase Subunit Bears a Deletion in Osteosclerotic (oc/oc) Mutants

A. Franchi
  • Fonction : Auteur
C. Trojani
  • Fonction : Auteur
Hugues Parrinello
  • Fonction : Auteur
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J Grosgeorge
  • Fonction : Auteur
Cédric Robert Robert
  • Fonction : Auteur
O. Jaillon
C. Poirier
  • Fonction : Auteur
P Gaudray
  • Fonction : Auteur
G F Carle
  • Fonction : Auteur

Résumé

Osteosclerosis (oc) is an autosomal recessive lethal mutation that impairs bone resorption by osteoclasts, and induces a general increase of bone density in affected mice. Genetic mapping of the oc mutation was used as a backbone in a positional cloning approach in the pericentromeric region of mouse chromosome 19. Perfect cosegregation of the osteope-trotic phenotype with polymorphic markers enabled the construction of a sequence-ready bacterial artificial chromosome (BAC) contig of this region. Genomic sequencing of a 200-kb area revealed the presence of the mouse homologue to the human gene encoding the osteoclast-specific 116-kDa subunit of the vacuolar proton pump. This gene was located recently on human 11q13, a genomic region conserved with proximal mouse chromosome 19. Sequencing of the 5 end of the gene in oc/oc mice showed a 1.6-kb deletion, including the translation start site, which impairs genuine transcription of this subunit. The inactivation of this osteoclast-specific vacuolar proton ATPase subunit could be responsible for the lack of this enzyme in the apical membranes of osteoclast cells in oc/oc mice, thereby preventing the resorption function of these cells, which leads to the osteopetrotic phenotype. (Bone 26:207-213; 2000)

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hal-02117516 , version 1 (02-05-2019)

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J.-C Scimeca, A. Franchi, C. Trojani, Hugues Parrinello, J Grosgeorge, et al.. The Gene Encoding the Mouse Homologue of the Human Osteoclast-Specific 116-kDa V-ATPase Subunit Bears a Deletion in Osteosclerotic (oc/oc) Mutants. BONE, 2000, ⟨10.1016/S8756-3282(99)00278-1⟩. ⟨hal-02117516⟩
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