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PMID: 15546001 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy.

The Journal of clinical investigation ·Vol. 114 ·No. 10 ·2004-11-00 ·Pages 1504-11

Hunter RB, Kandarian SC

Abstract

The intracellular signals that mediate skeletal muscle protein loss and functional deficits due to muscular disuse are just beginning to be elucidated. Previously we showed that the activity of an NF-kappaB-dependent reporter gene was markedly increased in unloaded muscles, and p50 and Bcl-3 proteins were implicated in this induction. In the present study, mice with a knockout of the p105/p50 (Nfkb1) gene are shown to be resistant to the decrease in soleus fiber cross-sectional area that results from 10 days of hindlimb unloading. Furthermore, the marked unloading-induced activation of the NF-kappaB reporter gene in soleus muscles from WT mice was completely abolished in soleus muscles from Nfkb1 knockout mice. Knockout of the B cell lymphoma 3 (Bcl3) gene also showed an inhibition of fiber atrophy and an abolition of NF-kappaB reporter activity. With unloading, fast fibers from WT mice atrophied to a greater extent than slow fibers. Resistance to atrophy in both strains of knockout mice was demonstrated clearly in fast fibers, while slow fibers from only the Bcl3(-/-) mice showed atrophy inhibition. The slow-to-fast shift in myosin isoform expression due to unloading was also abolished in both Nfkb1 and Bcl3 knockout mice. Like the soleus muscles, plantaris muscles from Nfkb1(-/-) and Bcl3(-/-) mice also showed inhibition of atrophy with unloading. Thus both the Nfkb1 and the Bcl3 genes are necessary for unloading-induced atrophy and the associated phenotype transition.

Keywords
NASA Discipline Musculoskeletal Non-NASA Center
MeSH Terms
Animals Female Genes, Reporter Hindlimb Suspension Mice Mice, Inbred Strains Mice, Knockout Muscle Fibers, Fast-Twitch/metabolism Muscle Fibers, Slow-Twitch/metabolism Muscle, Skeletal/metabolism Muscular Atrophy/etiology,metabolism NF-kappa B/metabolism NF-kappa B p50 Subunit Proto-Oncogene Proteins/genetics Time Factors Transcription Factors/genetics
Chemicals
NF-kappa B NF-kappa B p50 Subunit Proto-Oncogene Proteins Transcription Factors Nfkb1 protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hunter R Bridge
Department of Health Sciences, Boston University, Boston, Massachusetts 02215, USA.
Kandarian Susan C
Investigators
1 investigators, click to expand
Kandarian S C
Boston U, MA
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI21696
Published
2004-11-00
Pages
1504-11
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC525738
Subset
IM
Grants
NIAMS NIH HHS · R01 AR041705 · United States
NIAMS NIH HHS · R01 AR41705 · United States
External Links
PubMed source DOI: 10.1172/JCI21696 PMC Full Text View journal details
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