Animal models for inherited peripheral neuropathies

Martini, Rudolf

doi:10.1002/1097-4547(20000801)61:3<244::aid-jnr2>3.0.co;2-r

Cited by 43 publications

(32 citation statements)

References 69 publications

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“…These mice pathologically show more severe signs of demyelination with age than trembler‐j animals ( Henry et al, 1983 ; Heath et al, 1991 ) . As such, some authors have speculated that trembler‐j mice more closely resemble CMT1A, while the trembler mice resemble Dejerine–Sottas syndrome, a more severe hereditary human demyelinating peripheral neuropathy ( Low, 1977 ; Ionasescu et al, 1997 ; Martini, 1997 ) . Electrophysiological study of the trembler‐j mouse has been limited to one report ( Zielasek and Toyka, 1999 ) in which the authors described evidence of neuromyotonia in trembler‐j mice by needle electromyography, suggestive of ectopic impulse generation or ephaptic transmission between adjacent axons.…”

Section: Introductionmentioning

confidence: 99%

Nerve conduction abnormalities in the trembler‐j mouse: A model for Charcot‐Marie‐Tooth disease type 1A?

Meekins

Emery

Weiss

2004

J Peripheral Nervous Sys

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The trembler-j mouse is a spontaneously occurring, demyelinating mutant secondary to a point mutation involving a leucine for proline substitution in the first transmembrane domain of the peripheral-myelin protein-22 (PMP-22) gene. It is considered to be a model for Charcot-Marie-Tooth disease type 1A (CMT1A), largely based upon pathologic observations. However, functional studies demonstrating homology with CMT1A patients have not been documented. Sciatic nerve conduction was performed on 30 and 72-day-old wildtype and trembler-j mice in a blinded fashion. The findings in the mutants in both age groups were consistent with profound demyelination. Trembler-j mice appear to have a greater degree of motor nerve conduction slowing relative to human studies involving patients with PMP-22 gene duplication. Functionally, the trembler-j is a good murine model for CMT1A associated with an identical point mutation but may represent a more severe disease phenotype than CMT1A secondary to PMP-22 gene duplication.

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Section: Introductionmentioning

confidence: 99%

Nerve conduction abnormalities in the trembler‐j mouse: A model for Charcot‐Marie‐Tooth disease type 1A?

Meekins

Emery

Weiss

2004

J Peripheral Nervous Sys

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“…12,13 Although PMP22 is widely expressed, by far the largest amount of PMP22 is produced by myelinating Schwann cells. It is clear from both human studies 7 and animal models 14 that alteration in PMP22 gene dosage and expression has profound effects on the development and maintenance of peripheral nerves. 2,10 Consequently, the regulation of PMP22 gene expression has been the focus of therapeutic strategies for CMT1A.…”

mentioning

confidence: 99%

“…19 Of note, severely affected patients with CMT1 with identical mutations and nerve biopsy results showing alterations analogous to those detected in heterozygous Tr-J and Tr mice have been described. 14,20,21 The pathomechanism for how these mutations affect myelination remains unknown; however, recent studies have shown that posttranslational events, such as protein processing, trafficking, and accumulation in different intracellular compartments, are critical for myelination of Schwann cells. [22][23][24][25] Recent experiments in diverse disease animal models suggest that curcumin enables misfolded proteins to traverse from the endoplasmic reticulum (ER) to the plasma membrane, [26][27][28][29] concurrently reducing the cytotoxicity of the mutant protein.…”

mentioning

confidence: 99%

Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype of the Trembler-J Mouse: A Potential Therapy for Inherited Neuropathy

Khajavi¹,

Shiga²,

Wiszniewski³

et al. 2007

The American Journal of Human Genetics

129

101

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Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies.

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“…Mouse models of inherited neuropaties-There are a few mouse models of inherited neuropathy. A particular advantage of inherited neuropathy animal models is that the onset and progress of the disease can be much better characterised than in human patients, who are usually investigated only when symptoms have already developed [137]. However these models are not fully useful for the detection of the presence of pain, since the severe compromission of motor fibers due to the pathology does not allow the evaluation of the classical neuropathic pain…”

Section: 1mentioning

confidence: 99%

“…Mutations in the human Cx32 gene have been linked to the X-linked form of CMT (CMTX) [155]. Mice deficient in the gene for Cx32 show pathological alterations in peripheral nerves comparable to those seen in the CMTX patients [137].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Murine models of human neuropathic pain

Colleoni¹,

Sacerdote²

2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

105

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Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, and autoimmune diseases are examples of diseases that may cause neuropathic pain. Unfortunately no satisfactory treatment is yet available for this type of pain. This consideration has led to an explosion of interest for the underlying mechanisms, accompanied by a growing number of animal models. In recent years, most of the neuropathic pain models initially developed in the rat have been translated to mice in order to exploit the resource represented by genetically modified mice. Obviously the most useful animal models of pain would be ones in which the etiology of the pain would be endogenous and not induced by the experimenters: together with the classic models based on peripheral nerve ligation, in the last years other techniques are being developed that mimic more closely clinical pain syndromes, often by attempting to induce the disease associated to neuropathic pain. Although several variables must be taken into account when using animal models for mimicking clinical neuropathic pain, the huge number of models that are now reproducible and well characterized should help to reach important goals in the comprehension of mechanisms and to discover novel therapeutic target for this disease.

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Animal models for inherited peripheral neuropathies

Cited by 43 publications

References 69 publications

Nerve conduction abnormalities in the trembler‐j mouse: A model for Charcot‐Marie‐Tooth disease type 1A?

Nerve conduction abnormalities in the trembler‐j mouse: A model for Charcot‐Marie‐Tooth disease type 1A?

Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype of the Trembler-J Mouse: A Potential Therapy for Inherited Neuropathy

Murine models of human neuropathic pain

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