Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy

Cook, S. R.; Hooser, Blair; Williams, D. C.; Kortz, Gregg D.; Aleman, Monica R; Minor, Katie M.; Koziol, Jennifer; Friedenberg, Steven G.; Cullen, John W.; Shelton, G. Diane; Ekenstedt, Kari J.

doi:10.1016/j.nmd.2023.06.007

Cited by 5 publications

(3 citation statements)

References 96 publications

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“…Even if PolyPhen2 was developed for the determination of variants in human beings, the analysis was conducted by performing the query with the amino acid sequence of canine reference and the corresponding positions of the variants, thus utilizing the in silico prediction of PolyPhen2. PolyPhen2 has been previously used for this type of evaluation in canine specimens in the literature 10 – 12 . One variant was categorized as "benign".…”

Section: Resultsmentioning

confidence: 99%

Analysis of MDM2 and TP53 genes in canine liposarcoma

Muscatello,

de Biase,

Maloberti

et al. 2024

Sci Rep

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Canine liposarcoma is an uncommon tumor that shares morphological similarities with its human counterpart. In dogs, the genetic features of this tumor are unknown and, based on immunohistochemical studies, amplification of the gene MDM2 and the mutation of TP53 are suspected. In this study 51 cases of primary liposarcomas were immunohistochemically stained for MDM2 and p53 and subjected to fluorescent in situ hybridization and next-generation sequencing to detect MDM2 amplification and TP53 mutations, respectively. MDM2 and p53 were expressed in 21 and 6 cases, respectively. MDM2 amplification and TP53 mutations were identified in 10 and 15 cases, respectively. Statistical analysis revealed an association of the myxoid subtype and the mitotic count with p53 expression and TP53 mutation. No association was found between MDM2 amplification and MDM2 expression or tumor subtype. These results suggest that despite morphological similarities, canine liposarcoma differs from its human counterpart, for which MDM2 amplification is diagnostic for well differentiated and de-differentiated variants, and TP53 mutations are more common in pleomorphic liposarcoma rather than the myxoid one as occur in our cases. Furthermore, canine myxoid liposarcoma likely represents a distinct disease rather than a mere morphological variant.

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Section: Resultsmentioning

confidence: 99%

Analysis of MDM2 and TP53 genes in canine liposarcoma

Muscatello,

de Biase,

Maloberti

et al. 2024

Sci Rep

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“…The second variant involves the MPZ (myelin protein zero) gene and is a missense located in exon 3. The third variant is a C to T nonsense variant in exon 11 of the SH3TC2 (SH3 domain and tetratricopeptide repeats 2) gene [162].…”

Section: Leukodystrophies and Hypomyelinating Disordersmentioning

confidence: 99%

An Overview of Canine Inherited Neurological Disorders with Known Causal Variants

Cocostîrc,

Paștiu,

Pusta

2023

Animals

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Hereditary neurological conditions documented in dogs encompass congenital, neonatal, and late-onset disorders, along with both progressive and non-progressive forms. In order to identify the causal variant of a disease, the main two approaches are genome-wide investigations and candidate gene investigation. Online Mendelian Inheritance in Animals currently lists 418 Mendelian disorders specific to dogs, of which 355 have their likely causal genetic variant identified. This review aims to summarize the current knowledge on the canine nervous system phenes and their genetic causal variant. It has been noted that the majority of these diseases have an autosomal recessive pattern of inheritance. Additionally, the dog breeds that are more prone to develop such diseases are the Golden Retriever, in which six inherited neurological disorders with a known causal variant have been documented, and the Belgian Shepherd, in which five such disorders have been documented. DNA tests can play a vital role in effectively managing and ultimately eradicating inherited diseases.

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“…Hereditary peripheral neuropathies in humans are relatively common (e.g., Charcot–Marie–Tooth [CMT] disease affecting ∼1 in 2500 individuals), and likewise, LPN in the Labrador retriever is suggested to be a genetic disease (Jeffery et al., 2006), although causal genetic variants are not known. Moreover, multiple breed‐specific genetic associations have been identified in early‐onset versions of neurodegenerative conditions associated with laryngeal paralysis (Braund et al., 1994; Cook et al., 2023; Letko et al., 2020; Shelton et al., 2003).…”

Section: Introductionmentioning

confidence: 99%

Pathologic classification of a late‐onset peripheral neuropathy in a spontaneous Labrador retriever dog model

Anderson,

Chu,

Rylander

et al. 2024

J of Comparative Neurology

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Late‐onset peripheral neuropathy (LPN) is a heritable canine neuropathy commonly found in Labrador retrievers and is characterized by laryngeal paralysis and pelvic limb paresis. Our objective was to establish canine LPN as a model for human hereditary peripheral neuropathy by classifying it as either an axonopathy or myelinopathy and evaluating length‐dependent degeneration. We conducted a motor nerve conduction study of the sciatic and ulnar nerves, electromyography (EMG) of appendicular and epaxial musculature, and histologic analysis of sciatic and recurrent laryngeal nerves in LPN‐affected and control dogs. LPN‐affected dogs exhibited significant decreases in compound muscle action potential (CMAP) amplitude, CMAP area, and pelvic limb latencies. However, no differences were found in motor nerve conduction velocity, residual latencies, or CMAP duration. Distal limb musculature showed greater EMG changes in LPN‐affected dogs. Histologically, LPN‐affected dogs exhibited a reduction in the number of large‐diameter axons, especially in distal nerve regions. In conclusion, LPN in Labrador retrievers is a common, spontaneous, length‐dependent peripheral axonopathy that is a novel animal model of age‐related peripheral neuropathy that could be used for fundamental research and clinical trials.

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Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy

Cited by 5 publications

References 96 publications

Analysis of MDM2 and TP53 genes in canine liposarcoma

Analysis of MDM2 and TP53 genes in canine liposarcoma

An Overview of Canine Inherited Neurological Disorders with Known Causal Variants

Pathologic classification of a late‐onset peripheral neuropathy in a spontaneous Labrador retriever dog model

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