Connexin 32 is involved in mitosis

Saleh, María-Carla; Bordignon, Benoît; Fontés, Michel

doi:10.1002/glia.22279

Cited by 15 publications

(22 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we analyzed the impact of KN93 treatment on the behavioral phenotype already observed (Mones et al, 2012) in our transgenic models using the rotarod test. The S3 and G2 transgenic mouse lines present impairment appearing at about 7 months of age and progressing with age (Mones et al, 2012).…”

Section: Resultsmentioning

confidence: 92%

“…In a preceding article, we explore these different lines (Mones et al, 2012). We observed polyploidy in mitotic spread and an increase in nuclear volume in all transgenic lines, a result of mitotic instability that is frequently caused by centrosome overduplication.…”

Section: Resultsmentioning

confidence: 99%

“…The S3 and G2 transgenic mouse lines present impairment appearing at about 7 months of age and progressing with age (Mones et al, 2012). These lines were treated with a soluble form of KN93 (1.5 mg/kg i.p.…”

Section: Resultsmentioning

confidence: 99%

“…A machine manufactured by Bioseb was used for this purpose. A previously used procedure (Mones et al, 2012) was adapted and two velocities (15 and 25 rpm) were used. Briefly, each mouse underwent the same 5-day procedure.…”

Section: Methodsmentioning

confidence: 99%

“…These data suggested that Cx32 is involved in the control of mitotic stability. In addition, we noticed that the transgenic animals presented abnormal behavior on the rotarod (Mones et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

CamKII inhibitors reduce mitotic instability, connexon anomalies and progression of the in vivo behavioral phenotype in transgenic animals expressing a mutated Gjb1 gene

et al. 2014

Self Cite

View full text Add to dashboard Cite

Mutation in the Gjb1 gene, coding for a connexin (Cx32), is associated with an inherited peripheral neuropathic disorder (X-linked Charcot-Marie-Tooth, CMTX). Our previous work reported that transgenic animals expressing a human Gjb1 transgene present polyploidy and abnormal over-duplication of the centrosome, suggesting a role for Gjb1 in mitotic stability. In this article, we propose mechanisms by which mutations in Gjb1 induce mitotic instability and discuss its potential relation with the CMTX phenotype. We showed that transgenic cells exhibit CamKII over-stimulation, a phenomenon that has been linked to mitotic instability (polyploidy, nuclear volume and centrosome over-duplication), that is reversed by CamKII inhibitors. We also demonstrate that connexon activity is partially restored in transgenic cells with CamKII inhibitors. Our model supports the role for Pim1, a kinase that has been associated with genomic instability in cancers, in genomic instability in Cx32 mutations. Regarding in vivo phenotype, we showed that degradation on the rotarod test in our transgenic mice is significantly lowered by treatment with a CamKII inhibitor (KN93). This effect was seen in two lines with different point mutations in GJB1, and stopping the treatment led to degradation of the phenotype.

show abstract

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

CamKII inhibitors reduce mitotic instability, connexon anomalies and progression of the in vivo behavioral phenotype in transgenic animals expressing a mutated Gjb1 gene

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

Mechanisms and Treatments in Demyelinating CMT

Fridman

Saporta

2021

Neurotherapeutics

View full text Add to dashboard Cite

Demyelinating forms of Charcot-Marie-Tooth disease (CMT) are genetically and phenotypically heterogeneous and result from highly diverse biological mechanisms including gain of function (including dominant negative effects) and loss of function. While no definitive treatment is currently available, rapid advances in defining the pathomechanisms of demyelinating CMT have led to promising pre-clinical studies, as well as emerging clinical trials. Especially promising are the recently completed pre-clinical genetic therapy studies in PMP-22, GJB1, and SH3TC2-associated neuropathies, particularly given the success of similar approaches in humans with spinal muscular atrophy and transthyretin familial polyneuropathy. This article focuses on neuropathies related to mutations in PMP-22, MPZ, and GJB1, which together comprise the most common forms of demyelinating CMT, as well as on select rarer forms for which promising treatment targets have been identified. Clinical characteristics and pathomechanisms are reviewed in detail, with emphasis on therapeutically targetable biological pathways. Also discussed are the challenges facing the CMT research community in its efforts to advance the rapidly evolving biological insights to effective clinical trials. These considerations include the limitations of currently available animal models, the need for personalized medicine approaches/allele-specific interventions for select forms of demyelinating CMT, and the increasing demand for optimal clinical outcome assessments and objective biomarkers.

show abstract

Connexin Mutations in Pelizaeus–Merzbacher-Like Disease, Oculodentodigital Dysplasia and Related Diseases

Abrams

Orthmann-Murphy

2013

Gap Junctions in the Brain

View full text Add to dashboard Cite

Connexin 32 is involved in mitosis

Cited by 15 publications

References 33 publications

CamKII inhibitors reduce mitotic instability, connexon anomalies and progression of the in vivo behavioral phenotype in transgenic animals expressing a mutated Gjb1 gene

CamKII inhibitors reduce mitotic instability, connexon anomalies and progression of the in vivo behavioral phenotype in transgenic animals expressing a mutated Gjb1 gene

Mechanisms and Treatments in Demyelinating CMT

Connexin Mutations in Pelizaeus–Merzbacher-Like Disease, Oculodentodigital Dysplasia and Related Diseases

Contact Info

Product

Resources

About