Understanding the biological role of sialidase neu3 in tay-sachs disease mouse model için kapak resmi
Understanding the biological role of sialidase neu3 in tay-sachs disease mouse model
Başlık:
Understanding the biological role of sialidase neu3 in tay-sachs disease mouse model
Yazar:
Akyıldız Demir, Seçil, author.
Fiziksel Tanımlama:
xiv, 99 leaves: illustrarions, charts;+ 1 computer laser optical disc.
Özet:
Tay-Sachs disease is a severe lysosomal storage disorder characterized by mutations in the lysosomal β-Hexosaminidase A (HEXA) enzyme which converts GM2 to GM3 ganglioside. The GM2 ganglioside accumulation is observed predominantly in the neurons. The infants appear normal in their inborn time, but the progressive accumulation of undegraded GM2 results with death. Hexa-/- mice were created. However, they have a normal lifespan with no obvious neurological impairment until one year. It was thought that stored GM2 catabolized to GA2 using sialidase(s), which is further processed by HEXB. To determine the contribution of sialidase NEU3 to degradation of GM2, a mouse with combined deficiencies of Hexa and Neu3 genes was generated. The Hexa-/-Neu3-/- mice were healthy at birth, but they died between 1.5 and 5 months of age. Thin-layer chromatography and mass spectrometric analysis of the brains of Hexa-/-Neu3-/- mice revealed the abnormal accumulation of GM2. The progressive GM2 accumulation was also verified on testes, liver, and kidney of Hexa-/- Neu3-/- mice. GM2 accumulation in the brain leads to increased lysosomes with membranous cytoplasmic bodies, Purkinje cell depletion, cytoplasmic vacuolization, astrogliosis, and age-dependent lessening in neurons and oligodendrocytes. These mice have prominent disorders such as growth impairment, skeletal bones abnormalities, slow movement, tremors, anxiety and age-dependent loss in both memory and muscle strength. Consequently, the Hexa-/-Neu3-/- mice mimic the pathological, biochemical and clinical abnormalities of the Tay-Sachs patients, and useful model for the future understanding of cellular pathologies that drive the progression of the disease. They are a suitable model for the future pre-clinical testing of possible treatments
Yazar Ek Girişi:
Tek Biçim Eser Adı:
Thesis (Doctoral)--İzmir Institute of Technology: Molecular Biology and Genetics.

İzmir Institute of Technology: Molecular Biology and Genetics--Thesis (Doctoral).
Elektronik Erişim:
Access to Electronic Versiyon.
Ayırtma: Copies: