Canavan Disease (CD) is a devastating disease in children, caused by a recessive mutation in the enzyme aspartoacylase (ASPA). Using a KO mouse model, we will focus on two important aspects; 1) how ASPA deficiency regulates the development and maturation of neural cells and 2) does cell death and regeneration play a role and when is it's expression increased. All three questions will be addressed using the ASPA KO mouse model and comparing it to wild-type (WT) mice at different ages in early development. In order to examine the first question, KO and WT mice will be studied using various neural cell-specific markers. To address the second question, stem cell specific markers along with a cell death assay will be used to determine cell death and regeneration. While a lack of myelin is reported in autopsy tissues, it is anticipated that the lack of ASPA in OL cells is either directly or indirectly involved in CD pathogenesis and the death of OL. However, a chronological developmental study has not been possible in humans. Due to this limitation, it has not been possible to learn about early development of neural cells in CD patients, or to know if during early development the process of myelination was normal or impaired. It is not known if the neural cell regeneration and cell death that are seen is an age- or disease-mediated phenomenon. It is of great importance to begin to understand the mechanisms underlying disease progression in the mouse model in order to fill in the gaps of knowledge and potentially find a cure. However this understanding will also allow us to gain some insight into other neurodegenerative diseases. ? ? ?
