mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
Cardiac-specific deletion of the microtubule-binding protein CENP-F causes
dilated cardiomyopathy.
Authors Dees E, Miller PM, Moynihan KL, Pooley RD, Hunt RP, Galindo CL, Rottman JN,
Bader DM
Submitted By David Bader on 9/18/2012
Status Published
Journal Disease models & mechanisms
Year 2012
Date Published
Volume : Pages 5 : 468 - 480
PubMed Reference 22563055
Abstract CENP-F is a large multifunctional protein with demonstrated regulatory roles in
cell proliferation, vesicular transport and cell shape through its association
with the microtubule (MT) network. Until now, analysis of CENP-F has been
limited to in vitro analysis. Here, using a Cre-loxP system, we report the in
vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type
displaying high levels of CENP-F expression. Loss of CENP-F function in
developing myocytes leads to decreased cell division, blunting of trabeculation
and an initially smaller, thin-walled heart. Still, embryos are born at
predicted mendelian ratios on an outbred background. After birth, hearts lacking
CENP-F display disruption of their intercalated discs and loss of MT integrity
particularly at the costamere; these two structures are essential for cell
coupling/electrical conduction and force transduction in the heart. Inhibition
of myocyte proliferation and cell coupling as well as loss of MT maintenance is
consistent with previous reports of generalized CENP-F function in isolated
cells. One hundred percent of these animals develop progressive dilated
cardiomyopathy with heart block and scarring, and there is a 20% mortality rate.
Importantly, although it has long been postulated that the MT cytoskeleton plays
a role in the development of heart disease, this study is the first to reveal a
direct genetic link between disruption of this network and cardiomyopathy.
Finally, this study has broad implications for development and disease because
CENP-F loss of function affects a diverse array of cell-type-specific activities
in other organs.






Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.