| Co-Investigator(Kenkyū-buntansha) |
SOGAWA Kazuhiro Tohoku University, Graduate School of Science, Professor, 大学院・生命科学研究科, 教授 (80175421)
KOBAYASHI Akira Basic Medicine, Instructor, 基礎医学系, 講師 (50292214)
YAMAMOTO Masayuki Basic Medicine, Professor, 基礎医学系, 教授 (50166823)
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| Research Abstract |
Mouse BTEB and BTEB2 are transcription factors with three-time-repeated C_2H_2 zinc finger motif and bind the GC-box consensus sequence. In order to investigate their physiological functions, we have constructed targeting vectors by replacing the first exon with structural genes for β-gal in translational coding phase and neo and made BTEB- and BTEB2-deficient mice by homologous recombination technology using these targeting vectors. Concerning the BTEB-null mice, they, either male or female, were born apparently normal according to the Mendelian genetics from mating between heterozygous BTEB (+/-) dams and grew normal. The male and female offspring were fertile. Judging from the expression pattern of BTEB during the mouse development showing that the dramatically increased expression of BTEB was observed in Purkinye cells of the cerebellum and pyramidal cell layers of the hippocampus at P7 when synapses start to form in the brain, we investigated the memory and motor activity. Although general behavioral activities such as locomotion, rearing, and movement were not so much affected in the BTEB (-/-) mutant mice, they showed clearly reduced activity levels in rotorod and contextual fear conditioning tests, probably due to defective functions of the cerebellum, and hippocampus, respectively. On the other hand, homozygous BTEB-2 (-/-) mice were not born, while heterozygous BTEB2 (+/-) mice were born normally. Detailed analysis of embryos revealed that fertilized BTEB (-/-) oocytes developed apparently normally until E3.5 and died at E4.5. One of the causes for the early embryonic death was considered to be defective expression of FGF4 which is known to be important factor for the early embryonic development and was clarified to be a target gene of BTEB2.
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