Difference between revisions of "Model organisms"
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This site contains a list of model organisms to study human myopathies. Please feel free to edit/amend the list. | 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''''' | |
| + | {| class="wikitable sortable" | ||
| + | |- | ||
| + | ! mouse model !! description !! contact | ||
| + | |- | ||
| + | | [[#Mdx mutation|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/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|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|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 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 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|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|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 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]] || Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles|| Lieber | ||
| + | |- | ||
| + | | [[#VEGF knockout|VEGF knockout]] || Muscle specific VEGF knockout for the analysis of exercise injury. || Wagner | ||
| + | |- | ||
| + | | [[#Tmod1 knockout|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/mTR == | + | |
| + | === Mdx mutation === | ||
| + | MDX mutant mice do not express dystrophin and are used as a model system for Duchenne Muscular Dystrophy. <br /> | ||
| + | * More information: [http://jaxmice.jax.org/strain/001801.html More information on the mouse model (JAX lab)]<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy Duchenne Muscular Dystrophy]<br /> | ||
| + | * Contact: 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.<br /> | 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.<br /> | ||
| − | Read the publication [http://www.ncbi.nlm.nih.gov/pubmed/21145579 here].<br /> | + | * Read the publication [http://www.ncbi.nlm.nih.gov/pubmed/21145579 here].<br /> |
| − | '''Human disease''': [http://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy Duchenne Muscular Dystrophy]<br /> | + | * '''Human disease''': [http://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy Duchenne Muscular Dystrophy]<br /> |
| + | * Contact: 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. | ||
| + | * Read the publication [http://www.ncbi.nlm.nih.gov/pubmed/19584095 here] or find more information on an SDMRC funded Pilot Projects. More general information on the role of obscurin proteins for muscles can be found [http://slangelab.ucsd.edu/obscurin.html here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Limb-girdle_muscular_dystrophy Limb-girdle Muscular Dystrophy]<br /> | ||
| + | * Contact: 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. | ||
| + | * Read the publication [http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19864491/ here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Emery–Dreifuss_muscular_dystrophy Emery-Dreifuss muscular dystrophy (EDMD)]<br /> | ||
| + | * Contact: 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. | ||
| + | * Read the publication [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063916/ here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Nemaline_myopathy Nemaline Myopathy]<br /> | ||
| + | * Contact: 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. | ||
| + | * Read the publication [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198871/ here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Zaspopathy Zaspopathy]<br /> | ||
| + | * Contact: 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. | ||
| + | * Read the publication [http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=23975679 here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/FHL1 XMPMA (x-linked myopathy with postural muscle atrophy and generalized hypertrophy)]<br /> | ||
| + | * Contact: 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. | ||
| + | * Read the publication [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772735/ here].<br /> | ||
| + | * '''Human disease''': Laminopathy-related muscular dystrophies: [http://en.wikipedia.org/wiki/Emery–Dreifuss_muscular_dystrophy Emery-Dreifuss muscular dystrophy], limb girdle MD 1B <br /> | ||
| + | * Contact: 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. | ||
| + | * Read the publication [http://www.atsjournals.org/doi/abs/10.1165/rcmb.2006-0103OC?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&#.VDBTFildUcs here].<br /> | ||
| + | * '''Human disease''': Chronic obstructive lung disease, [http://en.wikipedia.org/wiki/Muscle_atrophy Muscle Wasting] <br /> | ||
| + | * 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 [http://ajpcell.physiology.org/cgi/pmidlookup?view=long&pmid=11003592 here].<br /> | ||
| + | * '''Human disease''': Chronic obstructive lung disease, [http://en.wikipedia.org/wiki/Desmin#Associated_diseases Desminopathy] <br /> | ||
| + | * 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 [http://www.sciencedirect.com/science/article/pii/S1569904805002557 here].<br /> | ||
| + | * '''Human disease''': Chronic disease and skeletal muscle function (COPD and CHF)<br /> | ||
| + | * 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 [http://jcb.rupress.org/content/189/1/95.long here], [http://jcb.rupress.org/content/194/1/105.long here], and [http://www.fasebj.org/content/28/1/408.long here].<br /> | ||
| + | * 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. | ||
| + | * Read the publication [http://www.sciencedirect.com/science/article/pii/S000634950902579X here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Hereditary_inclusion_body_myopathy Inclusion body myopathy type 3]<br /> | ||
| + | * Contact: Sanford Bernstein | ||
| + | |||
| + | |||
| + | ---- | ||
| + | |||
| + | == Human cells == | ||
| − | Contact: | + | === 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 [http://dx.doi.org/10.1002/mus.10446 here] and [http://onlinelibrary.wiley.com/doi/10.1002/mus.10247/abstract6 here].<br /> | ||
| + | * '''Human disease''': [http://en.wikipedia.org/wiki/Cerebral_palsy Cerebral Palsy]<br /> | ||
| + | * Contact: Andrea Domenighetti, Sam Ward, Rick Lieber | ||
Latest revision as of 16:34, 12 March 2015
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.
- More information: More information on the mouse model (JAX lab)
- Human disease: Duchenne Muscular Dystrophy
- Contact: 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.
- Read the publication here.
- Human disease: Duchenne Muscular Dystrophy
- Contact: 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.
- Read the publication here or find more information on an SDMRC funded Pilot Projects. More general information on the role of obscurin proteins for muscles can be found here.
- Human disease: Limb-girdle Muscular Dystrophy
- Contact: 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.
- Read the publication here.
- Human disease: Emery-Dreifuss muscular dystrophy (EDMD)
- Contact: 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.
- Read the publication here.
- Human disease: Nemaline Myopathy
- Contact: 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.
- Read the publication here.
- Human disease: Zaspopathy
- Contact: 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.
- Read the publication here.
- Human disease: XMPMA (x-linked myopathy with postural muscle atrophy and generalized hypertrophy)
- Contact: 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.
- Read the publication here.
- Human disease: Laminopathy-related muscular dystrophies: Emery-Dreifuss muscular dystrophy, limb girdle MD 1B
- Contact: 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.
- 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.
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.
- Read the publication here.
- Human disease: Inclusion body myopathy type 3
- Contact: Sanford Bernstein
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
