Colocalization Analysis of Peripheral Myelin Protein-22 and Lamin-B1 in the Schwann Cell Nuclei of Wt and TrJ Mice

Abstract

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.

Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture

“…Overall, in both cellular domains, PMP22 expression was higher in TrJ/+ SCs compared to +/+ SCs. This result is in line, not only with works reporting the existence of cytoplasmic aggregates of PMP22 in TrJ/+ nerves [29,69,83,84] but also in agreement with previous work from our group, which determines the PMP22 expression in +/+ and TrJ/+ SCs inside the nucleus [8,9].…”

“…PMP22 is highest expressed in the Schwann cells as a 160-amino-acid myelin glycoprotein, of 22 kDa, with four transmembrane domains, representing approximately 5% of the total compact myelin proteins [4]. However, central expression of PMP22 has also been signaled [5][6][7][8][9].…”

Irisin Attenuates Pathological Neovascularization in Oxygen-Induced Retinopathy Mice

“…The colocalization analysis of GFAP with VEGFA was performed employing the colocalization finder plugin of Image J software, as previously described. 32 …”

Impairment of auditory function in persons with type 2 diabetes mellitus depending on the level of peripheral myelin protein 22

“…З'ясовано, що специфічним маркером ступеня ураження нервових закінчень є периферичний мієліновий білок 22 (ПМБ 22, peripheral myelin protein 22, PMP 22) -ключовий компонент мієлінової оболонки, що синтезується шваннівськими клітинами і забезпечує міжклітинні контакти та потенціює фактор росту нервів та їх мієлінізацію [7,8]. На сьогодні підтверджена діагностична значущість зростання вмісту ПМБ 22 у сироватці крові як характерного лабораторного показника ступеня демієлінізації периферичних нервів, що свідчить про прогресування ускладнень з боку нервової системи [9,10].…”