• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

  • Oike Y
  • Hata A
  • Mamiya T
  • Kaname T
  • Noda Y
  • Suzuki M
  • Yasue H
  • Nabeshima T
  • Araki K
  • Yamamura K

Journal

Human molecular genetics

Publication Data

March 3, 1999

Associated Grants

None

Mesh Terms

  • 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