Towards brain-specific functions of histone deacetylases (HDACs) using genetic mouse models

Abstract

Epigenetic mechanisms and thus external transcriptional regulations are involved in a variety of physiological as well as pathophysiological processes. Important enzymes of the epigenetic machinery are the histone deacetylases (HDACs) which comprise an ancient family conserved from bacteria up to human beings.As the expression pattern throughout the adult murine brain and the mode of action of the specific isoforms of HDACs are unclear up to now, we conducted gene expression mapping to produce an atlas of the general distribution of HDAC1–11 within the murine brain using in situ hybridization analysis. Moreover, immunohistochemical double-labelling approaches will be performed to enable the identification of cell type specific expression.Besides, we intend to explore brain-specific roles of HDAC1 and HDAC3, two members of class I HDACs, by using neuronal cell lines and genetic mouse models. We have heterozygous lacZ reporter knockout mice and mice with conditional Hdac1 or Hdac3 alleles, respectively, which allow spatial and/or temporal gene inactivation as global deletion of either Hdac1 or Hdac3 results in embryonic lethality by E9.5. These animals are currently comprehensively phenotyped at a molecular and behavioral level. Thus, we intend to describe distinct in vivo roles of HDAC1 and HDAC3 within the brain under physiologic circumstances and roles related to processes like memory formation, emotional behavior and neurodegeneration. The results will be presented and discussed on the poster.