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Deletion of n icastrin Leads to Hypomyelination and Transcriptional Changes in Juvenile Mice
Author(s) -
Yamato Mizuho,
Zhu Yi,
Dries Daniel,
Yu Gang
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.813.6
Subject(s) - nicastrin , conditional gene knockout , protein subunit , biology , knockout mouse , transmembrane protein , neuroscience , microbiology and biotechnology , juvenile , central nervous system , presenilin , phenotype , medicine , disease , genetics , gene , alzheimer's disease , receptor
The γ‐secretase complex is a four‐subunit membrane‐bound protease complex that regulates a number of critical cellular functions through the cleavage of transmembrane substrate proteins. Of the four subunits, nicastrin is involved in substrate recruitment. Germline deletion of any of the four subunits leads to death during embryonic development. Previous work described a line of conditional knockout (cKO) mice in which nicastrin was knocked out of oligodendrocytes (OLs, the myelinating cells in the central nervous system). To examine the transcriptional changes that led to the pathological differences in juvenile mice, RNA‐Seq was performed. Here, we present the analysis of several genes with altered expression from the study using qPCR. Meanwhile, optic nerves were examined by electron microscopy (EM) to observe myelination during development. The results indicate that deletion of nicastrin from γ‐secretase leads to transcriptional changes and significantly affects myelination in the central nervous system of juvenile mice. Support or Funding Information This work was supported by the National Institute of Neurological Disorders and Stroke (R01 NS079796), the National Institute of Aging (AG029547, R01 AG023104 and F32 AG031625), the Welch Foundation (I‐1776), the Hartwell Foundation, and the Alzheimer's AssociationNational Institute of Neurological Disorders and Stroke (R01 NS079796), the National Institute of Aging (R01 AG023104 and F32 AG031625), the Welch Foundation (I‐1776), the Hartwell Foundation, and the Alzheimer's Association.