Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice

K R Gottshall1, J J Hunter, N Tanaka

  • 1Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0613, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 29, 1997
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Relationship between social support and autonomic function during a stress protocol in ulcerative colitis patients in remission.

Inflammatory bowel diseases·2011
Same author

Imaging retinal mosaics in the living eye.

Eye (London, England)·2011
Same author

Using attachment theory to understand illness behavior.

General hospital psychiatry·2001
Same author

Attachment and psychosomatic medicine: developmental contributions to stress and disease.

Psychosomatic medicine·2001
Same author

Effects of deletion of muscle LIM protein on myocyte function.

American journal of physiology. Heart and circulatory physiology·2001
Same author

Insecure attachment in a subgroup with ulcerative colitis defined by ANCA status.

Digestive diseases and sciences·2001

We developed a novel mouse model for hypertrophic cardiomyopathy (HCM) using echocardiographic selection of myosin light chain-Ras transgenic mice. These mice exhibit key features of human HCM, suggesting Ras-dependent pathways contribute to the disease.

Area of Science:

  • Cardiovascular Research
  • Genetics and Molecular Biology
  • Translational Medicine

Background:

  • Genetic and interindividual variability complicates the study of complex cardiac phenotypes.
  • Existing models do not fully recapitulate the multifaceted nature of human hypertrophic cardiomyopathy (HCM).

Purpose of the Study:

  • To develop a mouse model of HCM by selecting for enhanced ventricular hypertrophy using echocardiography.
  • To investigate the molecular, physiological, and pathological characteristics of this novel transgenic mouse model.
  • To compare the phenotype of the selected transgenic mice with wild-type and pressure overload models.

Main Methods:

  • Echocardiographic selection of myosin light chain (MLC)-Ras transgenic mice (RAS) for enhanced ventricular hypertrophy.

Related Experiment Videos

  • Comparison of RAS mice with wild-type (WT) and transverse aortic constriction (TAC) induced hypertrophy models.
  • Utilized novel miniaturized technology for in vivo intraventricular pressure and Doppler velocity gradient measurements.
  • Histological analysis for myofibrillar disarray and gene expression profiling for natriuretic peptides.

    • Main Results:

    • RAS mice exhibited significantly increased left ventricular (LV) wall thickness compared to WT and TAC groups.
    • In vivo intraventricular systolic Doppler velocity gradients were observed in 69% of RAS mice, absent in WT and TAC.
    • Extensive myofibrillar disarray (21.7% area fraction) was a hallmark of RAS mice, distinct from TAC (1.5%) and WT (0.0%).
    • RAS mice showed selective induction of natriuretic peptide genes in the LV, differing from pressure overload patterns.
    • Increased juvenile mortality was noted in offspring of echo-selected RAS parents.

    Conclusions:

    • Echocardiographic selection is effective for developing mouse models with specific cardiac phenotypes.
    • The inbred MLC-Ras transgenic mice accurately replicate key molecular, physiological, and pathological features of human HCM.
    • Ras-dependent pathways may play a significant role in certain forms of human HCM, similar to sarcomeric protein mutations.