Brain and bone damage in KARAP/DAP12 loss-of-function mice correlate with alterations in microglia and osteoclast lineages. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue American Journal of Pathology Année : 2005

Brain and bone damage in KARAP/DAP12 loss-of-function mice correlate with alterations in microglia and osteoclast lineages.

Serge Nataf
  • Fonction : Auteur
Adrienne Anginot
  • Fonction : Auteur
Carine Vuaillat
  • Fonction : Auteur
Luc Malaval
  • Fonction : Auteur
Emmanuel Chereul
  • Fonction : Auteur
Jean-Baptiste Langlois
Christiane Dumontel
  • Fonction : Auteur
Gaelle Cavillon
  • Fonction : Auteur
Christian Confavreux
  • Fonction : Auteur
Marlène Mazzorana
  • Fonction : Auteur
Laurence Vico
  • Fonction : Auteur
Marie-Franaçoise Belin
  • Fonction : Auteur
Eric Vivier
Pierre Jurdic
  • Fonction : Auteur

Résumé

Human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease, has been described to be associated with mutations affecting the immunoreceptor tyrosine-based activation motif-bearing KARAP/DAP12 immunoreceptor gene. Patients present bone fragilities and severe neurological alterations leading to presenile dementia. Here we investigated whether the absence of KARAP/DAP12-mediated signals in loss-of-function (KDelta75) mice also leads to bone and central nervous system pathological features. Histological analysis of adult KDelta75 mice brains revealed a diffuse hypomyelination predominating in anterior brain regions. As this was not accompanied by oligodendrocyte degeneration or microglial cell activation it suggests a developmental defect of myelin formation. Interestingly, in postnatal KDelta75 mice, we observed a dramatic reduction in microglial cell numbers similar to in vitro microglial cell differentiation impairment. Our results raise the intriguing possibility that defective microglial cell differentiation might be responsible for abnormal myelin development. Histomorphometry revealed that bone remodeling is also altered, because of a resorption defect, associated with a severe block of in vitro osteoclast differentiation. In addition, we show that, among monocytic lineages, KARAP/DAP12 specifically controls microglial and osteoclast differentiation. Our results confirm that KARAP/DAP12-mediated signals play an important role in the regulation of both brain and bone homeostasis. Yet, important differences exist between the symptoms observed in Nasu-Hakola patients and KDelta75 mice.

Domaines

Immunologie
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Dates et versions

hal-00165750 , version 1 (27-07-2007)

Identifiants

  • HAL Id : hal-00165750 , version 1
  • PUBMED : 15632019

Citer

Serge Nataf, Adrienne Anginot, Carine Vuaillat, Luc Malaval, Nassima Fodil, et al.. Brain and bone damage in KARAP/DAP12 loss-of-function mice correlate with alterations in microglia and osteoclast lineages.. American Journal of Pathology, 2005, 166 (1), pp.275-86. ⟨hal-00165750⟩

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