TY - JOUR
T1 - Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice
T2 - Implications for a dominant-negative mechanism
AU - Oike, Yuichi
AU - Hata, Akira
AU - Mamiya, Takayoshi
AU - Kaname, Tadashi
AU - Noda, Yukihiro
AU - Suzuki, Misao
AU - Yasue, Hirofumi
AU - Nabeshima, Toshitaka
AU - Araki, Kimi
AU - Yamamura, Ken Ichi
N1 - Funding Information:
We thank Dr John F. Maune for critical assistance in manuscript preparation, Dr T. Miyakawa and S. Oku for helpful advice, and Dr N. Hiro-oka, Dr M. Akizuki, Ms Y. Kiyonaga and Ms M. Tokushima for experimental assistance. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture of Japan.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/8.3.387
DO - 10.1093/hmg/8.3.387
M3 - Article
C2 - 9949198
AN - SCOPUS:0033018277
VL - 8
SP - 387
EP - 396
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 3
ER -