Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Gene Expression Deregulation in Postnatal Skeletal Muscle of TK2 Deficient Mice Reveals a Lower Pool of Proliferating Myogenic Progenitor Cells
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Sweden.
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Sweden.
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, e53698- p.Article in journal (Refereed) Published
Abstract [en]

Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

Place, publisher, year, edition, pages
2013. Vol. 8, no 1, e53698- p.
National Category
Medical and Health Sciences Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-194622DOI: 10.1371/journal.pone.0053698ISI: 000314759400069OAI: oai:DiVA.org:uu-194622DiVA: diva2:605799
Available from: 2013-02-15 Created: 2013-02-15 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

fulltext(913 kB)411 downloads
File information
File name FULLTEXT01.pdfFile size 913 kBChecksum SHA-512
0e435d22809cec0bc6ada7e6dc6e38a572662ce1444dfd789dd926e33de1e498bdcadeaac0e0713bce95e6fde35d5a10b3e84e659b64545043bf13dcc7a3eef2
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Höglund, Stefan
By organisation
Biochemistry
In the same journal
PLoS ONE
Medical and Health SciencesNatural Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 411 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 832 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf