Ultrastructural study of sciatic nerve in Ts1Cje mouse model for Down syndrome: an implication of peripheral nerve defects in hypotonia

Abstract

Trisomy 21 is chromosomal abnormality that occurs as a result of triplication of human chromosome 21 (Hsa21), a condition also known as Down syndrome (DS). Beside the intellectual disability and systems anomalies, motor dysfunction due to hypotonia has also been characterised in individuals with DS and yet, its aetiology remains unclear. Ts1Cje, a mouse model for DS, has a partial trisomy (Mmu16) homology to Hsa21, is widely used for DS research. This study investigated the morphological changes and degree of myelination in sciatic nerves of the Ts1Cje mice using both light and transmission electron microscopes processed images. The result showed no morphological difference in the sciatic nerve between the Ts1Cje and WT mice. The g ratio of the Ts1Cje mice was significantly (P<0.0001) higher compared to that of the WT mice. Two factors are known to determine the g ratio, the axonal diameter and the myeline thickness. There was no significant (P=0.2146) difference in the axonal diameter between the two genotypes. Interestingly, the myeline thickness was significantly (P<0.0001) thinner in nerve fibres of the Ts1Cje mice as compared to that of the WT mice. It is therefore concluded that, the hypomyelination in Ts1Cje mice may affect the conduction velocity which in turn affect their motor activity.