The Functional Studies of ZNF179 in Neurons in vitro and in vvo

Project: A - Government Institutionb - Ministry of Science and Technology

Project Details

Description

Znf179 is a member of the RING finger protein family. The expression of Znf179 is abundant in the brain and is regulated during brain development. Our previous study has first revealed the cellular function of Znf179 in neuronal differentiation. To study the physiological functions of Znf179 in vivo, we generated conventional Znf179 knockout mice and found that most of the Znf179 -/- embryos exhibited blood vascular defects and died in utero. Upon further investigation, we found that the survival rate of homozygous Znf179-knockout mice in 129/sv and C57BL/6 mixed genetic background was increased, providing opportunity to study the physiological function of Znf179 in the adult brain. Our preliminary data showed that the Znf179 -/- mice displayed impairment of brain functions including motor balance, and spatial learning and memory. In this proposal, using the Znf179 flox/flox mice and Znf179 overexpressed transgenic mice we have generated, we will further investigate the mechanisms of spatial learning and memory impairment in Znf179–deficient mice. The expression of factors known to be important for learning and memory such as CAMKII, ERK1/2, CREB and AMPA receptors will be examined by Western blot analysis and their expression pattern will be compared between wild type and Znf179 -/- mice in total lysate and different subcellular fractions such as post-synaptic density (PSD) fraction. We will further examine the changes of these factors between wild type and Znf179 -/- mice with or without training. Neuronal cultures isolated from the cortical/hippocampal tissues of E16.5 embryos will be used to investigate the differences in dendritic spine morphology and density of wild type and Znf179 knockout mice. In addition, we found that many of the genes responsible for scavenging reactive oxygen species were down-regulated in the hippocampus of Znf179 -/- mice. The potential neuroprotective effect and mechanism of Znf179 on oxidative stress will be further examined. Finally, the possible functional role of Znf179 in Huntington's disease will be examined by crossing the Znf179 transgenic mice with Huntington’s disease (HD) mice (R6/2). The pathological and behavioral parameters, such as neuronal intranuclear inclusion formation and motor performance deterioration will be compared between HD mice with or without Znf179 overexpression. Results of the proposed studies will provide important aspects for the study of Znf179 gene functions and new insights in neuronal diseases.
StatusFinished
Effective start/end date8/1/147/31/15