Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism.
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.
Pubmed ID: 9949198 RIS Download
Animals | Base Sequence | Behavior, Animal | CREB-Binding Protein | DNA Primers | Disease Models, Animal | Female | Genes, Dominant | Heterozygote | Humans | Male | Memory | Mice | Mice, Mutant Strains | Motor Activity | Mutagenesis, Insertional | Nuclear Proteins | Phenotype | Pregnancy | Rubinstein-Taybi Syndrome | Sequence Deletion | Trans-Activators