Strength and corticosteroid responsiveness of mdx mice is unchanged by RAG2 gene knockout

Paul T. Golumbek; Richard M. Keeling; Anne M. Connolly

doi:10.1016/j.nmd.2007.02.005

RAG2 gene knockout in mice causes fatigue

Muscle & Nerve ◽

10.1002/mus.20834 ◽

2007 ◽

Vol 36 (4) ◽

pp. 471-476 ◽

Cited By ~ 5

Author(s):

Paul T. Golumbek ◽

Richard M. Keeling ◽

Anne M. Connolly

Keyword(s):

Gene Knockout ◽

Rag2 Gene

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Amelioration of muscular dystrophy phenotype in mdx mice by inhibition of Flt1

10.1101/609735 ◽

2019 ◽

Author(s):

Mayank Verma ◽

Yuko Shimizu-Motohashi ◽

Yoko Asakura ◽

James Ennen ◽

Jennifer Bosco ◽

...

Keyword(s):

Endothelial Cell ◽

Muscular Dystrophy ◽

Knockout Mice ◽

Gene Knockout ◽

Functional Improvement ◽

Mdx Mice ◽

Vascular Density ◽

Dystrophic Muscle ◽

Skeletal Muscle Function ◽

Vegf Signaling

AbstractDuchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease in which the dystrophin coding for a membrane stabilizing protein is mutated. Recently, the vasculature has also shown to be perturbed in DMD and DMD model mdx mice. Data-mining DMD transcriptomics revealed the defects were correlated to a vascular endothelial growth factor (VEGF) signaling pathway. To reveal the relationship between DMD and VEGF signaling, mdx mice were crossed with constitutive (CAG/CreERTM:Flt1LoxP/LoxP) and endothelial cell-specific conditional gene knockout mice (Cdh5CreERT2:Flt1LoxP/LoxP) for Flt1 which is a decoy receptor for VEGF. Previous work demonstrated that heterozygous global Flt1 knockout mice increased vascular density and improved DMD phenotypes when crossed with DMD model mdx and mdx:utrn-/- mice. Here, we showed that while constitutive deletion of Flt1 is detrimental to the skeletal muscle function, endothelial cell-specific Flt1 deletion resulted in increased vascular density and improvement in the DMD-associated phenotype in the mdx mice. These decreases in pathology, including improved muscle histology and function, were recapitulated in mdx mice given anti-FLT1 peptides or monoclonal antibodies, which blocked VEGF-FLT1 binding. The histological and functional improvement of dystrophic muscle by FLT1 blockade provides a novel pharmacological strategy for the potential treatment of DMD.

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Fine structure of early degenerating myofibers in the tibialis anterior of young ‘MDX’ mouse

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010010367x ◽

1988 ◽

Vol 46 ◽

pp. 322-323

Author(s):

H.D. Geissinger ◽

C.K. McDonald-Taylor

Keyword(s):

Fine Structure ◽

Muscle Regeneration ◽

Tibialis Anterior ◽

Genetic Defect ◽

Mdx Mouse ◽

Mdx Mice ◽

Histopathological Changes ◽

Electron Microscopic ◽

Dystrophic Mouse ◽

Preliminary Study

A new strain of mice, which had arisen by mutation from a dystrophic mouse colony was designated ‘mdx’, because the genetic defect, which manifests itself in brief periods of muscle destruction followed by episodes of muscle regeneration appears to be X-linked. Further studies of histopathological changes in muscle from ‘mdx’ mice at the light microscopic or electron microscopic levels have been published, but only one preliminary study has been on the tibialis anterior (TA) of ‘mdx’ mice less than four weeks old. Lesions in the ‘mdx’ mice vary between different muscles, and centronucleation of fibers in all muscles studied so far appears to be especially prominent in older mice. Lesions in young ‘mdx’ mice have not been studied extensively, and the results appear to be at variance with one another. The degenerative and regenerative aspects of the lesions in the TA of 23 to 26-day-old ‘mdx’ mice appear to vary quantitatively.

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Regenerating myofibers in tibialis anterior muscles of young ‘MDX’ mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127943 ◽

1987 ◽

Vol 45 ◽

pp. 726-727

Author(s):

H. D. Geissinge ◽

L.D. Rhodes

Keyword(s):

Muscular Dystrophy ◽

Mouse Model ◽

Tibialis Anterior ◽

Physiological Activity ◽

Mdx Mice ◽

Mode Of Inheritance

A recently discovered mouse model (‘mdx’) for muscular dystrophy in man may be of considerable interest, since the disease in ‘mdx’ mice is inherited by the same mode of inheritance (X-linked) as the human Duchenne (DMD) muscular dystrophy. Unlike DMD, which results in a situation in which the continual muscle destruction cannot keep up with abortive regenerative attempts of the musculature, and the sufferers of the disease die early, the disease in ‘mdx’ mice appears to be transient, and the mice do not die as a result of it. In fact, it has been reported that the severely damaged Tibialis anterior (TA) muscles of ‘mdx’ mice seem to display exceptionally good regenerative powers at 4-6 weeks, so much so, that these muscles are able to regenerate spontaneously up to their previous levels of physiological activity.

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Production of prion gene knockout cow to prevent spontaneous bovine spongiform encephalopathy

Reproduction Abstracts ◽

10.1530/repabs.1.p052 ◽

2014 ◽

Author(s):

Noboru Manabe ◽

Ichiro Onoyama ◽

Junyou Li ◽

Yutaka Sendai ◽

Yoshito Aoyagi

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Gene Knockout ◽

Spongiform Encephalopathy ◽

Prion Gene

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Effect of taste receptor protein T1R3 on the development of islet tissue of the murine pancreas

Доклады Академии наук ◽

10.31857/s0869-56524841117-120 ◽

2019 ◽

Vol 484 (1) ◽

pp. 117-120

Author(s):

V. O. Murovets ◽

E. A. Sozontov ◽

T. G. Zachepilo

Keyword(s):

Parent Strain ◽

Gene Knockout ◽

Taste Receptor ◽

Morphological Characteristics ◽

Sweet Taste ◽

Pancreatic Tissue ◽

Receptor Protein ◽

Gene Encoding ◽

Islet Tissue ◽

Knockout Animals

Protein T1R3, the main subunit of sweet, as well as amino acid, taste receptor, is expressed in the epithelium of the tongue and gastro intestinal tract, in β–cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing witnesses of T1R3 involvement in control of carbohydrate and lipid metabolism, and control of production of incretines and insulin, have been determined. In the study on Tas1r3-gene knockout mouse strain and parent strain C57Bl/6J as control, priority data concerning the effect of T1R3 on the morphological characteristics of Langerhans islets in the pancreas, are obtained. In Tas1r3 knockout animals, it is found that the size of the islets and their density in pancreatic tissue are reduced, as compared to the parent strain. Additionally, a decrease of expression of active caspase-3 in islets of gene-knockouts is demonstrated. The obtained data show that the lack of a functional, gene encoding sweet-taste receptor protein causes a dystrophy of the islet tissue and associates to the development of pathological changes in the pancreas specific to type-2 diabetes and obesity in humans.

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