Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome.

Abstract:

:CBP is a transcriptional coactivator required by many transcription factors for transactivation. Rubinstein-Taybi syndrome, which is an autosomal dominant syndrome characterized by abnormal pattern formation, has been shown to be associated with mutations in the Cbp gene. Furthermore, Drosophila CBP is required in hedgehog signaling for the expression of decapentapleigic, the Drosophila homologue of bone morphogenetic protein. However, no direct evidence exists to indicate that loss of one copy of the mammalian Cbp gene affects pattern formation. Here, we show that various abnormalities occur at high frequency in the skeletal system of heterozygous Cbp-deficient mice resulting from a C57BL/6-CBA x BALB/c cross. In support of a conserved signaling pathway for pattern formation in insects and mammals, the expression of Bmp7 was found to be reduced in the heterozygous mutants. The frequency of the different abnormalities was significantly lower in a C57BL/6-CBA background, suggesting that the genetic background is an important determinant of the variability and severity of the anomalies seen in Rubinstein-Taybi syndrome patients.

authors

Tanaka Y,Naruse I,Maekawa T,Masuya H,Shiroishi T,Ishii S

doi

10.1073/pnas.94.19.10215

subject

Has Abstract

pub_date

1997-09-16 00:00:00

pages

10215-20

issue

19

eissn

0027-8424

issn

1091-6490

journal_volume

94

pub_type

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