| Autor: |
Di Tomaso MV; Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay., Vázquez Alberdi L; Laboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay., Olsson D; Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay., Cancela S; Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay., Fernández A; Laboratorio de Neurobiología Comparada, Departamento de Neurociencias Integrativas, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay., Rosillo JC; Laboratorio de Neurobiología Comparada, Departamento de Neurociencias Integrativas, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay., Reyes Ábalos AL; Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.; Unidad de Microscopía Electrónica de Barrido, Universidad de la República, Montevideo 11400, Uruguay., Álvarez Zabaleta M; Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay., Calero M; Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Unidad de Encefalopatías Espongiformes (UFIEC), 28029 Madrid, Spain.; Queen Sofia Foundation Alzheimer Center, CIEN Foundation, 28031 Madrid, Spain., Kun A; Laboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.; Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay. |
| Abstrakt: |
Myelination of the peripheral nervous system requires Schwann cells (SC) differentiation into the myelinating phenotype. The peripheral myelin protein-22 (PMP22) is an integral membrane glycoprotein, expressed in SC. It was initially described as a growth arrest-specific ( gas3 ) gene product, up-regulated by serum starvation. PMP22 mutations were pathognomonic for human hereditary peripheral neuropathies, including the Charcot-Marie-Tooth disease (CMT). Trembler-J (TrJ) is a heterozygous mouse model carrying the same pmp22 point mutation as a CMT1E variant. Mutations in lamina genes have been related to a type of peripheral (CMT2B1) or central (autosomal dominant leukodystrophy) neuropathy. We explore the presence of PMP22 and Lamin B1 in Wt and TrJ SC nuclei of sciatic nerves and the colocalization of PMP22 concerning the silent heterochromatin (HC: DAPI-dark counterstaining), the transcriptionally active euchromatin (EC), and the nuclear lamina (H3K4m3 and Lamin B1 immunostaining, respectively). The results revealed that the number of TrJ SC nuclei in sciatic nerves was greater, and the SC volumes were smaller than those of Wt. The myelin protein PMP22 and Lamin B1 were detected in Wt and TrJ SC nuclei and predominantly in peripheral nuclear regions. The level of PMP22 was higher, and those of Lamin B1 lower in TrJ than in Wt mice. The level of PMP22 was higher, and those of Lamin B1 lower in TrJ than in Wt mice. PMP22 colocalized more with Lamin B1 and with the transcriptionally competent EC, than the silent HC with differences between Wt and TrJ genotypes. The results are discussed regarding the probable nuclear role of PMP22 and the relationship with TrJ neuropathy. |
