Contraction force generated by tarsal joint flexion and extension in dogs with golden retriever muscular dystrophy

Kornegay, Joe N.; Bogan, Daniel J.; Bogan, Janet R.; Childers, Martin K.; Cundiff, Diane D.; Petroski, Gregory F.; Schueler, Ronald O.

doi:10.1016/s0022-510x(99)00118-5

Cited by 69 publications

(113 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[1][2][3][4][5][6] Animal positioning, limb placement and electrode placement are key variables that significantly impact results. In a preliminary study, mean alveolar concentration (MAC) values for isoflurane did not significantly affect force measurements (Schueler RO, Koch H, Kornegay JN, unpublished data, 1993).Hardware and software are commercially available and methods well-established.…”

Section: Discussionmentioning

confidence: 99%

<em>In Vivo</em> Canine Muscle Function Assay

Childers¹,

Grange²,

Kornegay³

2011

JoVE

Self Cite

View full text Add to dashboard Cite

We describe a minimally-invasive and reproducible method to measure canine pelvic limb muscle strength and muscle response to repeated eccentric contractions. The pelvic limb of an anesthetized dog is immobilized in a stereotactic frame to align the tibia at a right angle to the femur. Adhesive wrap affixes the paw to a pedal mounted on the shaft of a servomotor to measure torque. Percutaneous nerve stimulation activates pelvic limb muscles of the paw to either push (extend) or pull (flex) against the pedal to generate isometric torque. Percutaneous tibial nerve stimulation activates tibiotarsal extensor muscles. Repeated eccentric (lengthening) contractions are induced in the tibiotarsal flexor muscles by percutaneous peroneal nerve stimulation. The eccentric protocol consists of an initial isometric contraction followed by a forced stretch imposed by the servomotor. The rotation effectively lengthens the muscle while it contracts, e.g., an eccentric contraction. During stimulation flexor muscles are subjected to an 800 msec isometric and 200 msec eccentric contraction. This procedure is repeated every 5 sec. To avoid fatigue, 4 min rest follows every 10 contractions with a total of 30 contractions performed. Video LinkThe It is assumed that the hardware is connected to the computer that runs the DMC software, and that the system is calibrated. The software may be revised from time to time; therefore, instructions are provided below relevant to the current software version that we use. When the software is opened, it is already running.The user can initially write a protocol in DMC (e.g., to stimulate at 50 Hz for 1.5 s to produce an isometric tetanus) and the protocol can then be saved for subsequent use. We use two standard protocols: (1) isometric contraction protocol (e.g., twitch or tetanus); and (2) eccentric stretch-injury protocol. We start with the isometric contraction protocol for the twitch. To optimize the twitch, the Monitor Outputs screen is used; torque generated during the twitch can be observed as the electrodes are moved. When the maximum twitch response is achieved, the data are collected by returning to the main screen (select Continue) and selecting Begin and Done. Files are saved from the Save As pop-up window. With the electrodes maintained in the same position, a tetanus (50 Hz) is then collected and saved. When all isometric contractions are completed, the eccentric stretch-injury protocol can be loaded and run. Because there are a series of contractions to be executed in this protocol (10 contractions), on the main screen the Run One button is selected to reveal Run All status. Now when Begin is selected, a Run All Protocols pop up window appears that asks for the root file name and the directory into which the files are to be saved. Then, Start Protocol Series Test and Done are selected to initiate the eccentric protocol. The files are saved automatically into the selected Directory. Positioning the animal in the physiology rig1. Animal care and use committee (ACUC) guideline...

show abstract

Section: Discussionmentioning

confidence: 99%

<em>In Vivo</em> Canine Muscle Function Assay

Childers¹,

Grange²,

Kornegay³

2011

JoVE

Self Cite

View full text Add to dashboard Cite

show abstract

“…This large animal model of DMD offers a number of advantages that are not available to the mdx mice. 10,11 Besides muscle histopathology, the GRMD dogs exhibit clinical signs closely mimicking those observed in humans, for example, muscle atrophy, contractures, overt cardiomyopathy, premature death, and so on. More importantly, the dogs also have a much larger body mass than the mice, making the dogs more relevant to human DMD patients when assessing therapeutic doses of AAV vectors.…”

Section: Introductionmentioning

confidence: 97%

A canine minidystrophin is functional and therapeutic in mdx mice

Wang

Qiao

et al. 2008

Gene Ther

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is the most common and lethal genetic muscle disorder lacking a curative treatment. We wish to use the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog, a canine model of DMD, to investigate adeno-associated virus (AAV) vectormediated minidystrophin gene therapy. The dog model is useful in evaluating vector dose requirement and immunological consequences owing to its large size and outbred nature. In this study, we have cloned and constructed a canine minidystrophin gene vector. Owing to limited availability of the GRMD dogs, here we first examined the functions and therapeutic effects of the canine minidystrophin in the mdx mouse model. We observed efficient minigene expression without cellular immune responses in mdx mice after AAV1-cMinidys vector intramuscular injection. We also observed restoration of the missing dystrophin-associated protein complex (DPC) onto the sarcolemma, including sarcoglycans and dystrobrevin, and a partial restoration of a-syntrophin and neural nitric oxide synthase (nNOS). In addition, minidystrophin treatment ameliorated dystrophic pathology, such as fibrosis and myofiber central nucleation (CN). CN remained minimal (o2%) after AAV injection in the neonatal mdx mice and was reduced from more than 75% to about 25% after AAV injection in adult mdx mice. Finally, in vivo cell membrane leakage test with Evans blue dye showed that the canine minidystrophin could effectively protect the myofiber plasma membrane integrity. Our results, thus, demonstrated the functionality and therapeutic potential of the canine minidystrophin and paved its way for further testing in the GRMD dog model.

show abstract

“…Dentre os sinais clínicos observa-se a fraqueza muscular progressiva inicial de cintura pélvica e posteriormente de cintura escapular e com a evolução da doença, observa--se o quadro clínico de insuficiência respiratória e/ou cardíaca, a principal causa "mortis" na DMD (Caromano 1999, Kornegay et al 1999, Strober 2006. Os sinais clínicos respiratórios se exacerbam com o aumento da carga mecânica sustentada a cada movimento respiratório, pela musculatura respiratória já enfraquecida promovendo a redução da complacência pulmonar e da mobilidade da caixa torácica e, por conseguinte hipercapnia, hipoventilação pulmonar, hipoxemia (secundária a hipercapnia) e clearence de secreções (Araujo et al 2004).…”

Section: Introductionunclassified

Arquitetura comparativa dos pulmões de camundongos normais e afetados pela Distrofia Muscular de Duchenne

et al. 2015

View full text Add to dashboard Cite

RESUMO.-A Distrofia Muscular de Duchenne (DMD) é uma doença genética de caráter recessivo que caracterizada por fraqueza muscular progressiva de cintura pélvica e escapular evoluindo para insuficiência respiratória e, ou cardíaca. O camundongo mdx é um modelo amplamente utilizado para estudos da DMD. Apesar do fenótipo destes animais serem mais suave, estes apresentam o principal músculo respiratório, o diafragma com morfologia e bioquímica semelhante à DMD humana, fato este que pode comprometer a função respirató-ria e consequentemente os pulmões. Foi realizado um estudo anatômico descritivo do parênquima pulmonar dos pulmões de 5 animais modelo mdx comparando estes com os pulmões de 5 camundongos BALB/C57 (Mus musculus). Os pulmões foram analisados macroscopicamente e através de microscopia de luz e eletrônica de varredura. Os achados sugerem que o modelo mdx apresenta morfologia pulmonar semelhante aos camundongos BALB/C57 e que seu uso deve ser cauteloso e criterioso em ensaios clínicos que aborde este órgão.TERMOS DE INDEXAÇÃO: Distrofia muscular, Duchenne, mdx, morfologia pulmonar, anatomia respiratória. INTRODUÇÃOA anatomia descritiva constitui parte dos princípios primordiais da pesquisa, uma vez que esta descreve tecidos biológicos fornecendo dados morfológicos importantes para análises de estudos de afecções que envolvem alterações teciduais e reparo.A Distrofia Muscular de Duchenne (DMD) é uma doença neuromuscular, de origem hereditária de caráter recessivo, incidindo em meninos em 1 a cada 3500 nascidos. Sua evolução é rápida e severa caracterizada por uma mutação do gene que codifica a proteína 427 kDA chamada distrofina. A distrofina corresponde por cerca de apenas 0,002% da massa proteica da célula muscular estriada, e está localizada na superfície intracelular do sarcolema e se associa a várias glicoproteínas integrais da membrana, formando The Duchenne Muscular Dystrophy (DMD) is a recessive genetic disease characterized by progressive muscle weakness of the pelvic and scapular girdle and progressing to respiratory or heart failure. The mdx mouse is a model widely used for studies. Although they possess a milder phenotype, the morphology and biochemistry of the diaphragm are similar to human DMD. We performed a descriptive anatomical study of the pulmonary parenchyma of five mdx animal models and compared these with the lungs of 5 mice BALB/ C57 (Mus musculus). The findings suggest that the mdx model has morphological features similar to BALB/C57 mice and it must be used with caution in clinical trials which involve the lung.

show abstract

Contraction force generated by tarsal joint flexion and extension in dogs with golden retriever muscular dystrophy

Cited by 69 publications

References 26 publications

<em>In Vivo</em> Canine Muscle Function Assay

<em>In Vivo</em> Canine Muscle Function Assay

A canine minidystrophin is functional and therapeutic in mdx mice

Arquitetura comparativa dos pulmões de camundongos normais e afetados pela Distrofia Muscular de Duchenne

Contact Info

Product

Resources

About