Model organisms

From SDMRC
Jump to: navigation, search

This site contains a list of model organisms to study human myopathies. Please feel free to edit/amend the list.

Mouse models

Table of mouse models

mouse model description contact
Mdx mutation MDX mutant mice do not express dystrophin and are used as a model system for Duchenne Muscular Dystrophy. Alessandra Sacco mailto:asacco@sanfordburnham.org
mdx/mTR MDX mice lacking the RNA component of telomerase (mdx/mTR) have shortened telomeres in muscle cells and severe muscular dystrophy that progressively worsens with age. Alessandra Sacco mailto:asacco@sanfordburnham.org
Obscurin knockout The obscurin mouse develops a mild skeletal muscle myopathy, characterised by an age-dependent increase in centralised nuclei. Stephan Lange mailto:slange@ucsd.edu
nesprin-1 knockout Data suggest that Nesprin 1 may be involved in the pathogenesis of Emery-Dreifuss muscular dystrophy. Ju Chen mailto:juchen@ucsd.edu
nebulin knockout Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. Nebulin-deficient mice die within 8-11 d after birth, with symptoms including decreased milk intake and muscle weakness. Ju Chen mailto:juchen@ucsd.edu
Cypher knockout Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Ju Chen mailto:juchen@ucsd.edu
FHL1 knockout Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery-Dreifuss muscular dystrophy. Ju Chen mailto:juchen@ucsd.edu
Net25 knockout 6 nuclear envelope transmembrane proteins (NETs) are predicted to have important functions in muscle development and/or maintenance from their expression patterns during myoblast differentiation and in mouse tissues. Mutations in certain NETs cause muscular dystrophies and other disorders, but the disease mechanisms remain unclear. Gerace
SP-C/TNF-alpha over- expressing mouse SP-C/TNF-alpha mice exhibited increased levels of TNF-alpha in the circulation and increased endogenous TNF-alpha expression in skeletal muscle, potentially reflecting an amplificatory response to circulating TNF-alpha. Decreased muscle and body weights observed in SP-C/TNF-alpha mice were indicative of muscle wasting. Hogan, Wagner
Desmin knockout Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles Lieber
VEGF knockout Muscle specific VEGF knockout for the analysis of exercise injury. Wagner
Tmod1 knockout Global Tmod1 ablation results in embryonic lethality due to defects in cardiac myofibrillogenesis and development. We rescued the lethality of Tmod1-knockout mice by crossing these mice with mice overexpressing Tmod1 under the control of the cardiac-specific α-myosin heavy chain promoter, generating viable and fertile mice that lack Tmod1 in all tissues except the heart. Skeletal muscle from rescued Tmod1-knockout mice show compensatory translocation of Tmod3 from the sarcoplasmic reticulum to the thin filament pointed ends, resulting in defects in sarcoplasmic reticulum organization and actomyosin crossbridge formation. Velia Fowler mailto:velia@scripps.edu


Mdx mutation

MDX mutant mice do not express dystrophin and are used as a model system for Duchenne Muscular Dystrophy.

mdx/mTR

MDX mice lacking the RNA component of telomerase (mdx/mTR) have shortened telomeres in muscle cells and severe muscular dystrophy that progressively worsens with age.

Obscurin knockout

The obscurin mouse develops a mild skeletal muscle myopathy, characterised by an age-dependent increase in centralised nuclei.

nesprin-1 knockout

Data suggest that Nesprin 1 may be involved in the pathogenesis of Emery-Dreifuss muscular dystrophy.

nebulin knockout

Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. Nebulin-deficient mice die within 8-11 d after birth, with symptoms including decreased milk intake and muscle weakness.

Cypher knockout

Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles.

FHL1 knockout

Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery-Dreifuss muscular dystrophy.

Net25 knockout

6 nuclear envelope transmembrane proteins (NETs) are predicted to have important functions in muscle development and/or maintenance from their expression patterns during myoblast differentiation and in mouse tissues. Mutations in certain NETs cause muscular dystrophies and other disorders, but the disease mechanisms remain unclear.

SP-C/TNF-alpha over- expressing mouse

SP-C/TNF-alpha mice exhibited increased levels of TNF-alpha in the circulation and increased endogenous TNF-alpha expression in skeletal muscle, potentially reflecting an amplificatory response to circulating TNF-alpha. Decreased muscle and body weights observed in SP-C/TNF-alpha mice were indicative of muscle wasting.

  • Read the publication here.
  • Human disease: Chronic obstructive lung disease, Muscle Wasting
  • Contact: Hogan, Wagner

Desmin knockout

Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles.

  • Read the publication here.
  • Human disease: Chronic obstructive lung disease, Desminopathy
  • Contact: Lieber

VEGF knockout

Methods to study exercise are evolving from classically integrative organ approaches towards the more fundamental cellular reactions. While in vitro cellular and molecular methods are well established, only recently has in vivo molecular manipulation been widely used.

  • Read the publication here.
  • Human disease: Chronic disease and skeletal muscle function (COPD and CHF)
  • Contact: Wagner

Tmod1 knockout

Tmod1 knockout muscles exhibit compensatory translocation of Tmod3 from the sarcoplasmic reticulum to the thin filament pointed ends, resulting in defects in sarcoplasmic reticulum function and actin-myosin crossbridge interactions. Tmod1-knockout mice can be used to study the physiological importance of actin filament pointed-end capping in vivo.

  • Read the publications here, here, and here.
  • Contact: Fowler


Drosophila Models

Myosin Point Mutation

A Single Amino Acid Mutation in the Drosophila Myosin SH1 Domain Severely Affects Muscle Function, Myofibril Structure, Myosin Enzymatic Activity, and Actin Sliding Velocity.


Human cells

Cerebral Palsy Patient Cells

Spasticity represents a tremendous clinical and personal challenge. Patients suffer from upper motor neuron lesions due to diverse disorders such as static perinatal encephalopathy (cerebral palsy), stroke, degenerative diseases, head injury, and spinal cord injury.

  • Read the publication here and here.
  • Human disease: Cerebral Palsy
  • Contact: Andrea Domenighetti, Sam Ward, Rick Lieber
Retrieved from "http://sdmrc.ucsd.edu/~sdmrcwiki/index.php?title=Model_organisms&oldid=178"