Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: Implications for a dominant-negative mechanism

Yuichi Oike, Akira Hata, Takayoshi Mamiya, Tadashi Kaname, Yukihiro Noda, Misao Suzuki, Hirofumi Yasue, Toshitaka Nabeshima, Kimi Araki, Ken Ichi Yamamura

研究成果: Article査読

265 被引用数 (Scopus)

抄録

A mouse model of Rubinstein-Taybi syndrome (RTS) was generated by an insertional mutation into the cyclic AMP response element-binding protein (CREB)-binding protein (CBP) gene. Heterozygous CBP-deficient mice, which had truncated CBP protein (residues 1-1084) containing the CREB-binding domain (residues 462-661), showed clinical features of RTS, such as growth retardation (100%), retarded osseous maturation (100%), hypoplastic maxilla with narrow palate (100%), cardiac anomalies (15%) and skeletal abnormalities (7%). Truncated CBP is considered to have been acting during development as a dominant-negative inhibitor to lead to the phenotypes of RTS in mice. Our studies with step-through-type passive avoidance tests and with fear conditioning test showed that mice were deficient in long-term memory (LTM). In contrast, short-term memory (STM) appeared to be normal. These results implicate a crucial role for CBP in mammalian LTM. Our CBP(+/-) mice would be an excellent model for the study of the role of CBP in development and memory storage mechanisms.

本文言語English
ページ(範囲)387-396
ページ数10
ジャーナルHuman molecular genetics
8
3
DOI
出版ステータスPublished - 1999

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 遺伝学(臨床)

フィンガープリント

「Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: Implications for a dominant-negative mechanism」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル