Abstract
The steroid receptor coactivator (SRC) family contains three members that can enhance transcriptional activities of nuclear hormone receptors (NRs). To study the role of SRC-1 in brain development and function, we examined the spatial and temporal expression patterns of SRC-1 and characterized the phenotypes of brain development and function in SRC-1 knockout (SRC-1-/-) mice. In the adult, SRC-1 was highly expressed in the various brain areas and preferentially detected in Purkinje cells (PCs) in the cerebellum. SRC-2 was expressed at lower levels in most brain structures where SRC-1 was expressed. However, SRC-3 mRNA was detectable only in the hippocampus. Multiple behavioral tests revealed that SRC-1-/- mice exhibited moderate motor dysfunction. The time-course analysis revealed that the disruption of SRC-1 delayed the PC development at embryonic stages. However, the morphology of SRC-1-/- PCs developed to the same extents of wild type PCs at the neonatal stage when SRC-2 mRNA was significantly elevated in SRC-1-/- PCs, suggesting that SRC-2 may partially compensate the loss of SRC-1 function. In addition, SRC-1 was colocalized with various NRs and other coactivators in the specific brain regions, regulating hormonal action including sexual behavior. These results demonstrate the relative levels of individual SRC expression are dependent on specific brain regions and the degree of overlapping expression may determine their functional redundancy accompanied with hormonal action. [Jpn J Physiol 54 Suppl:S52 (2004)]
