Protein Expression of Canine and Feline Muscular Dystrophies

Salvadori, Claudia; Vattemi, Gaetano; Guglielmi, Valeria; Marini, Matteo; Tomelleri, Giuliano; Cantile, Carlo

doi:10.1016/j.tcam.2020.100500

Cited by 3 publications

(5 citation statements)

References 35 publications

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“…Histopathological, histochemical, as well as immunohistochemical studies were performed as described [ 69 , 70 , 71 ]. Briefly, cryosections (10 μm) and paraffin-embedded sections (4–6 μm) of longitudinal and transverse skeletal muscle biopsies were stained with hematoxylin & eosin (H&E), Engel’s modified Gomori, Masson-Trichrome Elastica van Gieson (EvG), oil red O, periodic acid Schiff and/or Tibor Pap silver impregnation stains.…”

Section: Methodsmentioning

confidence: 99%

Dystrophin (DMD) Missense Variant in Cats with Becker-Type Muscular Dystrophy

Hilton

Christen

Bilzer

et al. 2023

IJMS

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Muscular dystrophy due to dystrophin deficiency in humans is phenotypically divided into a severe Duchenne and milder Becker type. Dystrophin deficiency has also been described in a few animal species, and few DMD gene variants have been identified in animals. Here, we characterize the clinical, histopathological, and molecular genetic aspects of a family of Maine Coon crossbred cats with clinically mild and slowly progressive muscular dystrophy. Two young adult male littermate cats exhibited abnormal gait and muscular hypertrophy with macroglossia. Serum creatine kinase activities were highly increased. Histopathologically, dystrophic skeletal muscle exhibited marked structural changes including atrophic, hypertrophic, and necrotic muscle fibers. Immunohistochemistry showed irregularly reduced expression of dystrophin but the staining of other muscle proteins such as β- and γ-sarcoglycans as well as desmin was also diminished. Whole genome sequencing of one affected cat and genotyping of the littermate found both to be hemizygous mutant at a single DMD missense variant (c.4186C>T). No other protein-changing variants in candidate genes for muscular dystrophy were detected. In addition, one clinically healthy male littermate was hemizygous wildtype, while the queen and one female littermate were clinically healthy, but heterozygous. The predicted amino acid exchange (p.His1396Tyr) resides in a conserved central rod spectrin domain of dystrophin. Various protein modeling programs did not predict major disruption of the dystrophin protein by this substitution, but the altered charge of the region may still affect protein function. This study represents the first genotype-to-phenotype correlation of Becker-type dystrophin deficiency in companion animals.

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Section: Methodsmentioning

confidence: 99%

Dystrophin (DMD) Missense Variant in Cats with Becker-Type Muscular Dystrophy

Hilton

Christen

Bilzer

et al. 2023

IJMS

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“…While dogs with hereditary muscular dystrophies can initially be subclinical, most will develop progressive clinical signs such as muscle weakness, atrophy, or hypertrophy as well as exercise intolerance, gait abnormalities, hypertonicity, stiffness, or dysphagia. The adult age that hyperCKemia was first identified and the lack of clinical signs despite persistent severe hyperCKemia for 5 years in the dog reported here makes muscular dystrophic disorders such as dystrophinopathies, laminin α2 deficiency, sarcoglycanopathies, caveolin-3 trafficking alterations, calpain-3 deficiency, and collagen VI muscular dystrophy, unlikely ( 14 , 25 – 28 ). Similarly, the lack of development of any clinical signs also made an inflammatory process unlikely.…”

Section: Discussionmentioning

confidence: 81%

“…Necrotizing myopathies are generally associated with ≥ 1 clinical sign such as myalgia, fever, stilted gait, generalized weakness, decreased spinal reflexes, exercise intolerance, anorexia, lethargy, pigmenturia, or dysphagia and may be precipitated by factors such as drugs, toxins, snake bites, insect stings, ischemic myopathy, electrolyte disorders (e.g., hypokalemia), endocrinopathies, excessive exertion, hyperthermia, infectious diseases or are idiopathic ( 2 , 10 – 12 ). Hereditary muscular dystrophies could be associated with minimal clinical signs early in life but generally progress ( 13 , 14 ). Generalized and focal inflammatory myopathies are usually associated with moderate (i.e., 2,000–20,000 IU/L) and mild (i.e., 0–2,000 IU/L) increases in serum CK enzyme activity, respectively ( 2 , 8 ).…”

Section: Discussionmentioning

confidence: 99%

“…Muscle biopsies evaluated using a standard panel of histochemical stains and reactions (including fiber typing) as well as advanced immunohistochemical analysis for expression of relevant muscle proteins like dystrophin, dystrophin-associated proteins, laminins, and other proteins would have provided the best opportunity to identify the causal disease in the dog reported here but was declined by the owner ( 14 ). In humans, management of patients with increased serum CK enzyme activity and minimal or absent symptoms is a clinical dilemma.…”

Section: Discussionmentioning

confidence: 99%

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Case Report: Persistent Moderate-to-Severe Creatine Kinase Enzyme Activity Elevation in a Subclinical Dog

et al. 2021

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A 4-year-old, male-castrated, mixed breed dog was presented for a routine wellness examination at which time a moderate increase in serum creatine kinase (CK) enzyme activity (hyperCKemia) (15,137 IU/L; reference interval 10–200 IU/L), and moderate increases in alanine transaminase and aspartate aminotransferase enzyme activities were first identified. There was no history of clinical abnormalities (e.g., lethargy, lameness, anorexia, dysphagia, weakness, gait abnormalities, or exercise intolerance) and the physical examination was unremarkable. The dog was screened for several relevant potential infectious diseases known to cause inflammatory myopathies and was treated empirically with clindamycin. The serum total CK enzyme activity remained increased, which prompted recommendations for an echocardiogram, electromyogram (EMG), and muscle biopsy acquisition. The echocardiogram and electrocardiographic monitoring were unremarkable. The EMG and muscle biopsies were declined by the owner. The dog was evaluated several times in the subsequent 5 years and remained subclinical with unremarkable physical examinations despite a persistent moderate-to-severe hyperCKemia. Differential diagnoses considered most likely in this dog were an occult/latent hereditary muscular dystrophic disorder or idiopathic hyperCKemia, a phenomenon not yet reported in the veterinary literature. This report describes for the first time, clinical and diagnostic features of a subclinical dog with persistent moderate-to-severe hyperCKemia.

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“…Histopathological, histochemical, as well as immunohistochemical studies were performed as described [69][70][71]. Briefly, cryosections (10 µm) and paraffin-embedded sections (4-6 µm) of longitudinal and transverse skeletal muscle biopsies were stained with hematoxylin & eosin (H&E), Engel's modified Gomori, Masson-Trichrome Elastica van Gieson (EvG), oil red O, periodic acid Schiff and/or Tibor Pap silver impregnation stains.…”

Section: Histological and Immunohistological Skeletal Muscle Investig...mentioning

confidence: 99%