
Joe N KornegayTexas A&M University | TAMU · Department of Veterinary Integrative Biosciences
Joe N Kornegay
DVM, PhD
About
264
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Introduction
Additional affiliations
April 2012 - June 2019
Texas A&M University
Position
- Professor
October 2006 - April 2012
January 1994 - October 2006
Publications
Publications (264)
The occurrence of severe adverse events (SAEs) in patients with Duchenne muscular dystrophy (DMD), X-linked myotubular myopathy (XLMTM), and other neuromuscular diseases treated with adeno-associated virus (AAV) constructs has prompted studies to improve the safety and efficacy of gene therapy. Physicians have weighed the medical tenet of “first, d...
Background: Duchenne muscular dystrophy (DMD) and genetically homologous golden retriever muscular dystrophy (GRMD) are X-linked conditions causing progressive muscle wasting and cardiomyopathy. We previously defined a DMD-like dilated cardiomyopathy in adult GRMD dogs. The goal of this study was to extend our work and characterize the early natura...
Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with fatal muscle degeneration and atrophy. Patients have progressive reductions in skeletal muscle strength and resistance to eccentric muscle stretch. We assessed tibiotarsal joint (TTJ) flexor and extensor force dynamics, and resistance of dystrophic mus...
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retrie...
Background
Duchenne muscular dystrophy (DMD) is an X-linked inherited myopathy that causes progressive skeletal and cardiac muscle disease. Heart lesions were described in the earliest DMD reports, and cardiomyopathy is now the leading cause of death. However, diagnostics and treatment for cardiomyopathy have lagged behind those for appendicular an...
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the DMD gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the DMD reading frame have received regulatory approval as commer...
We have examined the effects of intravenous (IV) delivery of rAAVrh74.MHCK7.GALGT2 in the golden retriever muscular dystrophy (GRMD) model of Duchenne Muscular Dystrophy (DMD). After baseline testing, GRMD dogs were treated at 3 months of age and reassessed at 6 months. This 3–6 month age range is a period of rapid disease progression, thus offerin...
Duchenne's muscular dystrophy (DMD) is a severe muscle wasting disorder characterized by the loss of dystrophin expression, muscle necrosis, inflammation and fibrosis. Ongoing muscle regeneration is impaired by persistent cytokine stress, further decreasing muscle function. Patients with DMD rarely survive beyond their early 20s, with cardiac and r...
There is a great demand for accurate non‐invasive measures to better define the natural history of disease progression or treatment outcome in Duchenne muscular dystrophy (DMD) and to facilitate the inclusion of a large range of participants in DMD clinical trials. This review aims to investigate which MRI sequences and analysis methods have been u...
Introduction: Duchenne muscular dystrophy (DMD) and the genetically homologous model, golden retriever muscular dystrophy (GRMD), are x-linked conditions that cause progressive muscle wasting and cardiomyopathy. We previously defined a late onset DMD-like dilated cardiomyopathy in adult GRMD dogs and aimed to extend that work to young dogs used for...
Respiratory disease is a leading cause of morbidity in people with Duchenne muscular dystrophy and also occurs in the golden retriever muscular dystrophy (GRMD) model. We have previously shown that adult GRMD dogs have elevated expiratory flow as measured non-invasively during tidal breathing. This abnormality likely results from increased chest an...
[This corrects the article DOI: 10.1371/journal.pone.0228072.].
Duchenne muscular dystrophy (DMD) is a lethal, X-chromosome linked muscle-wasting disease affecting about 1 in 3500–6000 boys worldwide. Myofibre necrosis and subsequent loss of muscle mass are due to several molecular sequelae, such as inflammation and oxidative stress. We have recently shown increased neutrophils, highly reactive oxidant hypochlo...
[This corrects the article DOI: 10.1371/journal.pone.0194485.].
The availability of an in vitro canine cell line would reduce the need for dogs for primary in vitro cell culture and reduce overall cost in pre-clinical studies. An immortalized canine muscle cell line, named Myok9, from primary myoblasts of a normal dog has been developed by the authors. Immortalization was performed by SV40 viral transfection of...
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that abolish the expression of dystrophin protein. Dogs with the genetic homologue, golden retriever muscular dystrophy dog (GRMD), have a splice site mutation that leads to skipping of exon 7 and a stop codon in the DMD transcript. Gene editing via homology-directed repair (H...
The essential product of the Duchenne muscular dystrophy (DMD) gene is dystrophin¹, a rod-like protein² that protects striated myocytes from contraction-induced injury3,4. Dystrophin-related protein (or utrophin) retains most of the structural and protein binding elements of dystrophin⁵. Importantly, normal thymic expression in DMD patients⁶ should...
Background:
Duchenne muscular dystrophy (DMD) is an X‐linked disease that causes progressive muscle weakness. Affected boys typically die from respiratory or cardiac failure. Golden retriever muscular dystrophy (GRMD) is genetically homologous with DMD and causes analogous skeletal and cardiac muscle disease. Previous studies have detailed features...
Introduction:
Golden retriever muscular dystrophy (GRMD) is a spontaneous X-linked canine model of Duchenne muscular dystrophy (DMD) that resembles the human condition. Muscle percentage index (MPI) is proposed as an imaging biomarker of disease severity in GRMD.
Methods:
To assess MPI, we used MRI data acquired from nine GRMD samples using a 4....
Therapies for Duchenne muscular dystrophy (DMD) must first be tested in animal models to determine proof-of-concept, efficacy, and importantly, safety. The murine and canine models for DMD are genetically homologous and most commonly used in pre-clinical testing. Although the mouse is a strong, proof-of-concept model, affected dogs show more analog...
The authors would like to correct the following information concerning Conflict of Interest.
Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve...
Introduction
Golden retriever muscular dystrophy (GRMD), an X‐linked recessive disorder, causes similar phenotypic features to Duchenne muscular dystrophy (DMD). There is currently a need for a quantitative and reproducible monitoring of disease progression for GRMD and DMD.
Methods
To assess severity in the GRMD, we analyzed texture features extr...
Mice lacking the sarcolemmal protein dystrophin, designated mdx, have been widely used as a model of Duchenne muscular dystrophy. Dystrophic mdx mice as they mature develop notable morphological abnormalities to their neuromuscular junctions, the peripheral cholinergic synapses responsible for activating muscle fibers. Most obviously the acetylchol...
Identification of tSCs.
Confocal maximum intensity projection images of a P66 WT mouse NMJ. Arrowheads indicate S100:eGFP positive cells with nuclei in the fluorescent somata near the AChR rich endplate. Not all cells are indicated. These were considered tSCs for tSC counts. Composite image in red-AChR, green-S100:eGFP positive cells, gray-nuclei....
Motor axon varicosities in GRMD NMJs.
Confocal maximum intensity projection images of an adult GRMD dog NMJ. Arrows indicate bulbous varicosities of motor axons that synapse on the AChR endplate. Composite image in red-AChR, cyan-motor axon labeled with neurofilament and synaptic vesicle protein antibodies. Scale bar = 20 μm2.
(TIF)
Chart of significant differences in NMJ categorization following in vivo two-color BTX experiments (P38 WT myofiber damage and IC).
Comparisons within groups. 2-Way ANOVA with Bonferroni post-hoc test. Red boxes indicate redundancy. Black boxes indicate comparisons of the same categories. * P < 0.05. ** P < 0.01. *** P < 0.001.
(PDF)
NMJ Characterization and Reproducibility (40X).
Maximum intensity projection images of P38 mdx NMJs following in vivo two-color BTX method. In composite BTX-1 is pseudocolored red and BTX-2 green. Yellow indicates strong colocalization. Black arrows denote stable, continuous junctions. Black arrow heads denote stable, fragmented junctions. White ar...
NMJ Characterization and Reproducibility (20X).
Maximum intensity projection images of P38 and P66, mdx and WT NMJs following in vivo two-color BTX method. In composite BTX-1 is pseudocolored red and BTX-2 green. White arrows show examples of dynamic, continuous junctions. White arrow heads denote dynamic, fragmented junctions. Scale bar = 50 μm.
(...
Chart of significant differences in NMJ categorization following in vivo two-color BTX experiments (P38 WT and mdx).
Comparisons within genotypes. 2-Way ANOVA with Bonferroni post-hoc test. Red boxes indicate redundancy. Black boxes indicate comparisons of the same categories. * P < 0.05. ** P < 0.01. *** P < 0.001.
(PDF)
Chart of significant differences in NMJ categorization following in vivo two-color BTX experiments (P38 mdx myofiber damage and IC).
Comparisons within groups. 2-Way ANOVA with Bonferroni post-hoc test. Red boxes indicate redundancy. Black boxes indicate comparisons of the same categories. * P < 0.05. ** P < 0.01. *** P < 0.001.
(PDF)
Chart of significant differences in NMJ categorization following in vivo two-color BTX experiments (P38 mdx denervation and IC).
Comparisons within groups. 2-Way ANOVA with Bonferroni post-hoc test. Red boxes indicate redundancy. Black boxes indicate comparisons of the same categories. * P < 0.05. ** P < 0.01. *** P < 0.001.
(PDF)
3D rotation of P66 mdx NMJ.
3D maximum intensity projection of confocal stack. 0.5 μm gap between collection slices interpolated via Image J 3D Projection tool. BTX-1 pseudocolored red. BTX-2 pseudo colored green. DAPI nuclear label pseudocolored gray. Note the occurrence of a central chain of nuclei running within the myofiber directly under the d...
Objective:
Histology is often used as a gold standard to evaluate non-invasive imaging modalities such as MRI. Spatial correspondence between histology and MRI is a critical step in quantitative evaluation of skeletal muscle in golden retriever muscular dystrophy (GRMD). Registration becomes technically challenging due to non-orthogonal histology...
Duchenne muscular dystrophy (DMD) is a fatal Xlinked muscle disorder caused by mutations in the dystrophin gene with a consequence of progressive degeneration of skeletal and cardiac muscle. Golden retriever muscular dystrophy (GRMD) is a spontaneous X-linked canine model of DMD with similar effects. Due to high soft-tissue contrast images, MRI is...
Background:
Boys with Duchenne muscular dystrophy (DMD) have DMD gene mutations, with associated loss of the dystrophin protein and progressive muscle degeneration and weakness. Corticosteroids and palliative support are currently the best treatment options. The long-term benefits of recently approved compounds such as eteplirsen and ataluren rema...
Duchenne muscular dystrophy (DMD) causes progressive disability in 1 of every 5,000 boys due to the lack of functional dystrophin protein. Despite much advancement in knowledge about DMD disease presentation and progression—attributable in part to studies using mouse and canine models of the disease–current DMD treatments are not equally effective...
List of nonsynonymous SNVs.
All identified nonsynonymous SNVs are listed in the worksheet labeled “nonsynonymous”, while those included in top 10 up- and down-regulated DEGs are featured on the worksheet labeled “Included in Top10 lists”.
(XLSX)
Top 10 DEGs with associated log2 fold changes and q-values.
(XLS)
Results for gene ontology and pathway analysis for comparisons across fast, slow, and control dogs.
(XLS)
Introduction:
Duchenne muscular dystrophy (DMD) and golden retriever muscular dystrophy (GRMD) are X-linked disorders caused by mutations in the DMD gene. Autophagy was recently identified as a secondary therapeutic target for DMD. We hypothesized that autophagy would be reduced in GRMD.
Methods:
Autophagic gene and protein expression was assess...
Purpose: Metabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD)...
A workshop took place in 2015 to follow up TREAT-NMD activities dedicated to improving quality in the preclinical phase of drug development for neuromuscular diseases. In particular, this workshop adressed necessary future steps regarding common standard experimental protocols and the issue of improving the translatability of preclinical efficacy s...
Introduction:
Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN might share a molecular network with myostatin (MSTN).
Methods:
Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in vitro studies w...
Introduction: Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN). Methods: Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in-vitro studies were e...
Duchenne muscular dystrophy (DMD†) is an X-chromosome-linked disorder and the most common
monogenic disease in people. Affected boys are diagnosed at a young age, become non-ambulatory by
their early teens, and succumb to cardiorespiratory failure by their thirties. Despite being a monogenic
condition resulting from mutations in the DMD gene, affec...
Background:
Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the l...
Duchenne Muscular Dystrophy (DMD) is a genetic disorder caused by dystrophin protein deficiency. Muscle biopsy is the gold standard to determine the disease severity and progression. MRI has shown potential for monitoring disease progression or assessing the treatment effectiveness. In this study, multiple quantitative MRI parameters were used to c...
Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of the protein dystrophin. The absence of dystrophin leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or...
Background
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to skeletal muscle dysfunction. Metho...
Dystrophin is a key cytoskeletal protein coded by the Duchenne muscular dystrophy (DMD) gene located on the X-chromosome. Truncating mutations in the DMD gene cause loss of dystrophin and the classical DMD clinical
syndrome. Spontaneous DMD gene mutations and associated phenotypes occur in several other species. The
mdx mouse model and the golden r...
Data S1. Results from HMMER Search of Reference Proteomes Using Exon 2 Peptide Sequence of Dog LOC612257 as Query
Each species is provided in a separate sheet. Detailed information for each hit is provided, and hits remaining after each filtering criteria was applied are indicated in separate columns.