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

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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
Publication statusPublished - 04-03-1999

Fingerprint

Rubinstein-Taybi Syndrome
CREB-Binding Protein
Phenotype
Cyclic AMP Response Element-Binding Protein
Long-Term Memory
Protein Binding
Proteins
Palate
Maxilla
Short-Term Memory
Fear
Carrier Proteins
Mutation
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Oike, Y., Hata, A., Mamiya, T., Kaname, T., Noda, Y., Suzuki, M., ... 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.
Oike, Yuichi ; Hata, Akira ; Mamiya, Takayoshi ; Kaname, Tadashi ; Noda, Yukihiro ; Suzuki, Misao ; Yasue, Hirofumi ; Nabeshima, Toshitaka ; Araki, Kimi ; Yamamura, Ken Ichi. / Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice : Implications for a dominant-negative mechanism. In: Human molecular genetics. 1999 ; Vol. 8, No. 3. pp. 387-396.
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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.",
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Oike, Y, Hata, A, Mamiya, T, Kaname, T, Noda, Y, Suzuki, M, Yasue, H, Nabeshima, T, Araki, K & Yamamura, KI 1999, 'Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: Implications for a dominant-negative mechanism', Human molecular genetics, vol. 8, no. 3, pp. 387-396.

Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice : Implications for a dominant-negative mechanism. / Oike, Yuichi; Hata, Akira; Mamiya, Takayoshi; Kaname, Tadashi; Noda, Yukihiro; Suzuki, Misao; Yasue, Hirofumi; Nabeshima, Toshitaka; Araki, Kimi; Yamamura, Ken Ichi.

In: Human molecular genetics, Vol. 8, No. 3, 04.03.1999, p. 387-396.

Research output: Contribution to journalArticle

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

PY - 1999/3/4

Y1 - 1999/3/4

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.

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