Mice carrying an analogous heterozygous dynamin 2 K562E mutation that causes neuropathy in humans develop predominant characteristics of a primary myopathy

Abstract

Some mutations affecting dynamin 2 (DNM2) can cause dominantly inherited Charcot–Marie–Tooth (CMT) neuropathy. Here, we describe the analysis of mice carrying the DNM2 K562E mutation which has been associated with dominant-intermediate CMT type B (CMTDIB). Contrary to our expectations, heterozygous DNM2 K562E mutant mice did not develop definitive signs of an axonal or demyelinating neuropathy. Rather, we found a primary myopathy-like phenotype in these mice. A likely interpretation of these results is that the lack of a neuropathy in this mouse model has allowed the unmasking of a primary myopathy due to the DNM2 K562E mutation which might be overshadowed by the neuropathy in humans. Consequently, we hypothesize that a primary myopathy may also contribute to the disease mechanism in some CMTDIB patients. We propose that these findings should be considered in the evaluation of patients, the determination of the underlying disease processes and the development of tailored potential treatment strategies.

Recognising the potential of large animals for modelling neuromuscular junction physiology and disease

“…an axonal or demyelinating neuropathy, characteristic of the human disease (Pereira et al, 2020). Another study documented severe vocal fold paresis in humans, as a rare and sometimes life-threatening clinical feature of CMT type 2, resulting from autosomal dominant mutations of the canonical Notch ligand Jagged1 gene (or JAG1).…”

The prion protein is not required for peripheral nerve de- and remyelination after crush injury

“…Surgery was performed on the right hind limb of two-month-old female WT and Prnp ZH3/ZH3 mice as described previously [ 22 , 23 ]. Briefly, mice were injected with buprenorphinum (Temgesic, 0.1 mg/kg of bodyweight) prior to surgery.…”

“…Tissue was embedded in Epon using standard procedures. Further steps were performed as described [ 23 ]. Briefly, 99 nm sections were collected on ITO coverslips (Optics Balzers).…”

The prion protein is not required for peripheral nerve repair after crush injury

“…Surgery was performed on the right hind limb of two-month-old female WT and Prnp ZH3/ZH3 mice as described previously (17,18). Briefly, mice were injected with buprenorphinum (Temgesic, 0.1 mg/kg of bodyweight) prior to surgery.…”

“…Tissue was embedded in Epon using standard procedures. Further steps were performed as described (18). Briefly, 99 nm sections were collected on ITO coverslips (Optics Balzers).…”