Drp2-KO Mouse

Drp2, short for dystrophin-related protein 2, is a member of the dystrophin gene family. It is similar in structure to certain short C-terminal isoforms of dystrophin and dystrophin-related protein 1 (DRP1 or utrophin). Encoded in humans by a 45 kb gene located on Xq22, Drp2 is expressed mainly in the brain, spinal cord, and some peripheral tissues [3,4]. In Schwann cells, it forms Cajal bands with periaxin and dystroglycan, and is involved in stabilizing and limiting the radial growth of myelin [2].

In a cross-sectional retrospective observational study of 9 Spanish Charcot-Marie-Tooth disease (CMT) patients, 7 families with 4 different likely pathogenic germline variants in DRP2 were identified. Men with hemizygous DRP2 variants had an intermediate form of CMT, while heterozygous women were asymptomatic. Symptoms included lower limb weakness, multimodal sensory loss, and nerve echography showed an increase in the cross-sectional area of nerve roots and proximal nerves [1]. In mouse models, Drp2-null Schwann cells had disrupted appositions and Cajal bands, focal hypermyelination, and concomitant demyelination, but did not have the short internodal lengths and reduced nerve conduction velocity seen in periaxin-deficient mice, indicating distinct roles of Drp2 and periaxin in Schwann cell growth [2].

In conclusion, Drp2 plays a crucial role in the stability and growth regulation of myelin in Schwann cells. The study of Drp2, especially through mouse models, has enhanced our understanding of its role in CMT, a sensory and motor length-dependent neuropathy. These findings may contribute to better understanding of the disease mechanism and potentially guide future therapeutic strategies for CMT [1,2].

References:

1. Sivera, Rafael, Pelayo-Negro, Ana L, Jericó, Ivonne, Apellániz-Ruiz, María, Sevilla, Teresa. 2024. Expanding the Clinical Spectrum of DRP2-Associated Charcot-Marie-Tooth Disease. In Neurology, 102, e209174. doi:10.1212/WNL.0000000000209174. https://pubmed.ncbi.nlm.nih.gov/38513194/

2. Sherman, Diane L, Wu, Lai Man N, Grove, Matthew, Gillespie, C Stewart, Brophy, Peter J. . Drp2 and periaxin form Cajal bands with dystroglycan but have distinct roles in Schwann cell growth. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 32, 9419-28. doi:10.1523/JNEUROSCI.1220-12.2012. https://pubmed.ncbi.nlm.nih.gov/22764250/

3. Roberts, R G, Freeman, T C, Kendall, E, Bone, Q, Bobrow, M. . Characterization of DRP2, a novel human dystrophin homologue. In Nature genetics, 13, 223-6. doi:. https://pubmed.ncbi.nlm.nih.gov/8640231/

4. Dixon, A K, Tait, T M, Campbell, E A, Roberts, R G, Freeman, T C. . Expression of the dystrophin-related protein 2 (Drp2) transcript in the mouse. In Journal of molecular biology, 270, 551-8. doi:. https://pubmed.ncbi.nlm.nih.gov/9245586/