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

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalHuman molecular genetics
Volume8
Issue number3
DOIs
Publication statusPublished - 01-01-1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: Implications for a dominant-negative mechanism'. Together they form a unique fingerprint.

  • Cite this

    Oike, Y., Hata, A., Mamiya, T., Kaname, T., Noda, Y., Suzuki, M., Yasue, H., Nabeshima, T., Araki, K., & Yamamura, K. I. (1999). Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: Implications for a dominant-negative mechanism. Human molecular genetics, 8(3), 387-396. https://doi.org/10.1093/hmg/8.3.387