Molecular characterization and gene disruption of a novel zinc-finger protein, HIT-4, expressed in rodent brain

作者：Tanabe Yasutaka; Hirano Akiko; Iwasato Takuji; Itohara Shigeyoshi; Araki Kazuaki; Yamaguchi Tsuyoshi; Ichikawa Tomio; Kumanishi Toshiro; Aizawa Yoshifusa; Takahashi Hitoshi; Kakita Akiyoshi; Nawa Hiroyuki^*

来源：Journal of Neurochemistry, 2010, 112(4): 1035-1044.

DOI：10.1111/j.1471-4159.2009.06525.x

• alternative splicing
• degeneration
• gene targeting
• seizure
• vacuolization
• zinc-finger protein

To identify a novel regulatory factor involved in brain development or synaptic plasticity, we applied the differential display PCR method to mRNA samples from NMDA-stimulated and un-stimulated neocortical cultures. Among 64 cDNA clones isolated, eight clones were novel genes and one of them encodes a novel zinc-finger protein, HIT-4, which is 317 amino acid residues (36-38 kDa) in length and contains seven C(2)H(2) zinc-finger motifs. Rat HIT-4 cDNA exhibits strong homology to human ZNF597 (57% amino acid identity and 72% homology) and identity to rat ZNF597 at the carboxyl region. Furthermore, genomic alignment of HIT-4 cDNA indicates that the alternative use of distinct promoters and exons produces HIT-4 and ZNF597 mRNAs. Northern blotting revealed that HIT-4 mRNA (similar to 6 kb) is expressed in various tissues such as the lung, heart, and liver, but enriched in the brain, while ZNF597 mRNA (similar to 1.5kb) is found only in the testis. To evaluate biological roles of HIT-4/ZNF597, targeted mutagenesis of this gene was performed in mice. Homozygous (-/-) mutation was embryonic lethal, ceasing embryonic organization before cardiogenesis at embryonic day 7.5. Heterozygous (+/-) mice were able to survive but showing cell degeneration and vacuolization of the striatum, cingulate cortex, and their surrounding white matter. These results reveal novel biological and pathological roles of HIT-4 in brain development and/or maintenance.

• 出版日期2010-2