- Titel
- A proximo-distal characterization of disease pathogenesis in a model of Charcot-Marie-Tooth disease type 1A
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-1041665
- Datum der Einreichung
- 27.03.2025
- Datum der Verteidigung
- 19.03.2026
- Abstract (DE)
- Charcot-Marie-Tooth disease type 1A (CMT1A) is a slowly progressive and distally pronounced hereditary neuropathy. Caused by a duplication of a chromosome segment harboring the PMP22 gene, patients experience muscle weakness, deformities of hand and feet and walking difficulties due to a- and dysmyelination as well as secondary axonal loss. While the underlying genetic etiology of CMT1A is known, the spatial and temporal of disease development is not yet fully understood. Strikingly, histological degeneration is observed to occur in proximal nerves first, clinical symptoms start affecting the body distally. Therefore, this study systematically investigates proximal (ventral and dorsal root) and distal (femoral and saphenous nerve) nerves in a murine CMT1A model at different time points, combining histological, functional and behavioral analyses. It was shown that across all analyses, the motor ventral root was most strongly affected. Already at P18 it contained less myelinated and more hypo- and amyelinated axons as compared to the other nerves. This finding was consistent throughout time, whereas the predominantly motor femoral nerve was mainly altered at a young age compared to WT nerves. Neurofilament spacing was significantly reduced in both young mutant motor nerves as well as the aged ventral root, regardless of axon caliber and corroborated in amyelinated axons. Long-term gait analysis showed alterations in gait symmetry, body posture and coordination in CMT1A mice. This study does not only provide new insights into the unequal disease progression in motor vs sensory and proximal vs distal nerves, but further includes detailed descriptions of ultrastructural pathologies in a CMT1A mouse model. Moreover, the obtained results of WT animals are highly valuable for further related research requiring information of healthy nerves.
- Freie Schlagwörter (EN)
- CMT1A, neuropathy
- Klassifikation (DDC)
- 610
- Den akademischen Grad verleihende / prüfende Institution
- Universität Leipzig, Leipzig
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-1041665
- Veröffentlichungsdatum Qucosa
- 27.04.2026
- Dokumenttyp
- Dissertation
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY-NC-ND 4.0