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Conditional mouse models to study developmental and pathophysiological gene function in muscle.

B R Wamhoff1, S Sinha, G K Owens

  • 1Molecular Physiology and Biological Physics, The Robert M. Berne Cardiovascular Research Center, The University of Virginia, 415 Lane Road, Medical Research Building 5, Room 1226, P.O. Box 801394, Charlottesville VA 22908, USA.

Handbook of Experimental Pharmacology
|January 6, 2007
PubMed
Summary

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Conditional mouse models using Cre-loxP systems enable gene function studies in muscle. Challenges include cell plasticity and varying gene recombination efficiency, requiring rigorous confirmation for accurate physiological effect assessment.

Area of Science:

  • Muscle biology
  • Genetics
  • Developmental biology

Background:

  • Conditional mouse models are crucial for studying gene function in skeletal, cardiac, and vascular smooth muscle in vivo.
  • These models often employ muscle-specific promoters and Cre-loxP systems, including tamoxifen-inducible CreER for temporal control.

Purpose of the Study:

  • To review conditional mouse model systems for studying gene function in muscle.
  • To highlight challenges in Cre-mediated gene targeting in different muscle types, particularly vascular smooth muscle (SMC).
  • To emphasize the need for rigorous confirmation of recombination and physiological effects.

Main Methods:

  • Utilizing muscle-specific/selective promoter-enhancers.
  • Employing site-specific DNA recombinases (e.g., Cre-loxP).

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  • Incorporating temporal control via fusion proteins (e.g., CreER systems).

    • Main Results:

    • Vascular SMCs exhibit plasticity, complicating gene targeting with SMC marker promoters.
    • Gene targeting efficiency varies due to chromatin state affecting floxed loci sensitivity to Cre.
    • Confirmation of recombination degree is essential, considering tissue multicellularity.

    Conclusions:

    • Conditional mouse models are powerful tools for muscle gene function research.
    • Understanding muscle cell-specific challenges, like vascular SMC plasticity and chromatin-dependent recombination, is critical.
    • Rigorous validation of genetic modifications is necessary to accurately interpret physiological outcomes in muscle research.