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Series GSE56570 Query DataSets for GSE56570
Status Public on Apr 08, 2014
Title Comparison of genes regulated in P0 Klhl40 WT and KO skeletal muscle
Organism Mus musculus
Experiment type Expression profiling by array
Summary Nemaline myopathy (NM) is a congenital myopathy that can result in lethal muscle dysfunction and is thought to be a disease of the sarcomere thin filament. Recently, several proteins of unknown function have been implicated in NM, and their role in the disease remains unresolved. Here, we demonstrate that loss of a muscle-specific protein, Klhl40, results in a nemaline-like myopathy in mice that closely phenocopies the muscle abnormalities observed KLHL40 deficient patients. We show that Klhl40 dynamically localizes to the sarcomere I-band and A-band and binds to Nebulin (Neb), a protein frequently implicated in NM, as well as a putative thin filament protein, Lmod3. Klhl40 belongs to the BTB-BACK-Kelch (BBK) family of proteins, some of which have been previously shown to promote degradation of their substrates. In contrast, we find that Klhl40 promotes stability of Neb and Lmod3 and blocks Lmod3 ubiquitination. Accordingly, loss of Klhl40 reduces Neb and Lmod3 protein in skeletal muscle of mice and KLHL40 deficient patients. Because loss of sarcomere thin filament proteins is a frequent cause of NM, our data establishes a possible molecular basis for NM in KLHL40 deficient patients by establishing a novel pro-stability function of Klhl40 for Neb and Lmod3.
 
Overall design Total RNA was harvested from quadriceps muscle of three Klhl40 WT (control) and three Klhl40 KO mice. Each KO mouse was sacrificed with a corresponding WT littermate. Tissues were also taken at 0 days of age to minimize confounding gene changes occurring due to malnourishment as the phenotype worsens.
 
Contributor(s) Ankit G
Citation(s) 24960163
Submission date Apr 07, 2014
Last update date Jan 16, 2019
Contact name Ankit Garg
E-mail(s) ankitgarg2025@gmail.com
Organization name UT Southwestern Medical Center
Department Molecular Biology
Lab Eric N. Olson
Street address 6000 Harry Hines Blvd, NA 8.500
City Dallas
State/province TX
ZIP/Postal code 75235
Country USA
 
Platforms (1)
GPL6887 Illumina MouseWG-6 v2.0 expression beadchip
Samples (6)
GSM1364045 P0 Quadriceps Klhl40 WT 1
GSM1364046 P0 Quadriceps Klhl40 WT 2
GSM1364047 P0 Quadriceps Klhl40 WT 3
Relations
BioProject PRJNA243932

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE56570_Non-normalized_data.txt.gz 3.3 Mb (ftp)(http) TXT
GSE56570_RAW.tar 15.8 Mb (http)(custom) TAR
Raw data are available on Series record
Processed data included within Sample table

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