help button home button Am J Pathol ASIP 2008 Summer Academy, Molecular Methcanisms of Human Disease: Injury, Inflammation, and Tissue Repair
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nataf, S.
Right arrow Articles by Jurdic, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nataf, S.
Right arrow Articles by Jurdic, P.
(American Journal of Pathology. 2005;166:275-286.)
© 2005 American Society for Investigative Pathology

Brain and Bone Damage in KARAP/DAP12 Loss-of-Function Mice Correlate with Alterations in Microglia and Osteoclast Lineages

Serge Nataf*, Adrienne Anginot{dagger}, Carine Vuaillat*, Luc Malaval{ddagger}, Nassima Fodil§, Emmanuel Chereul, Jean-Baptiste Langlois, Christiane Dumontel*, Gaelle Cavillon*, Christian Confavreux*, Marlène Mazzorana{dagger}, Laurence Vico{ddagger}, Marie-Franaçoise Belin*, Eric Vivier§, Elena Tomasello§ and Pierre Jurdic{dagger}

From INSERM U433,* Faculté Laennec, Lyon; UMR 5161 CNRS/ENS, Unité Mixte de la Recherche Institut National de la Recherche Agronomique/Centre National de la Recherche Scientifique 1237,{dagger} Ecole Normale Supérieure, Lyon; Plate-forme ANIMAGE (Rhône-Alpes Genopole), Bat. Cermep, Lyon; Centre d’Immunologie de Marseille-Luminy,§ CNRS-INSERM, Université de la Méditerranée, Marseille; and Laboratoire de Biologie du Tissue Osseux INSERM E0366,{ddagger} Faculté de Médecine, Université Jean Monnet, Saint-Etienne, France.

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 (K{Delta}75) mice also leads to bone and central nervous system pathological features. Histological analysis of adult K{Delta}75 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 K{Delta}75 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 K{Delta}75 mice.




This article has been cited by other articles:


Home page
 Infect. Immun.Home page
K. J. Carpenter, K. F. Buckland, Z. Xing, and C. M. Hogaboam
Intrapulmonary, Adenovirus-Mediated Overexpression of KARAP/DAP12 Enhances Fungal Clearance during Invasive Aspergillosis
Infect. Immun., December 1, 2005; 73(12): 8402 - 8406.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.