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Neurogenetics
Published in: neurogenetics 4/2015

01-10-2015 | Original Article

Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease

Authors: Atsushi Sasaki, Akiyoshi Kakita, Kunihiro Yoshida, Takuya Konno, Takeshi Ikeuchi, Shintaro Hayashi, Hidenori Matsuo, Kei Shioda

Published in: Neurogenetics | Issue 4/2015

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Abstract

Nasu-Hakola disease (NHD) is a form of presenile dementia associated with sclerosing leukoencephalopathy and polycystic lipomembranous osteodysplasia. This extremely rare inherited disease is caused by mutations in either DAP12 or TREM2. The present study was designed to assess the relationship between DAP12/TREM2 genotype, mRNA and protein expression levels by both Western blotting and immunohistochemistry, and the tissue distribution and pathomorphological phenotype of the microglia. Molecular genetic testing performed in three NHD cases confirmed that two cases had mutations in DAP12 and that one case carried a mutation in TREM2. Protein levels were analyzed in four cases. Interestingly, significant DAP12 expression was found in numerous microglia in one NHD case with a homozygous DAP12 single-base substitution, and both real-time PCR and Western blotting confirmed the finding. In contrast, levels of both DAP12 and TREM2, respectively, were much lower in the other cases. Immunohistochemistry using established microglial markers revealed consistently mild activation of microglia in the cerebral white matter although there was no or only little expression of DAP12 in three of the NHD cases. The highly different expression of DAP12 represents the first description of such variable expressivity in NHD microglia. It raises important questions regarding the mechanisms underlying dementia and white matter damage in NHD.
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Metadata
Title
Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease
Authors
Atsushi Sasaki
Akiyoshi Kakita
Kunihiro Yoshida
Takuya Konno
Takeshi Ikeuchi
Shintaro Hayashi
Hidenori Matsuo
Kei Shioda
Publication date
01-10-2015
Publisher
Springer Berlin Heidelberg
Published in
Neurogenetics / Issue 4/2015
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-015-0451-3

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