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Faithful tissue-specific expression of the human chromosome 21-linked COL6A1 gene in BAC-transgenic mice

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Abstract

We created transgenic mice with a bacterial artificial chromosome (BAC) containing the human COL6A1 gene. In high-copy and low-copy transgenic lines, we found correct temporal and spatial expression of COL6A1 mRNA, paralleling the expression of the murine Col6a1 gene in a panel of nine adult and four fetal organs. The only exception was the fetal lung, in which the transgene was expressed poorly compared with the endogenous gene. Expression of COL6A1 mRNA from the transgene was copy number-dependent, and the increased gene dosage correlated with increased production of collagen VI alpha 1 in skin and heart, as indicated by Western blotting and immunohistochemistry. COL6A1 maps to Chromosome 21 and this gene has been a candidate for contributing to cardiac defects and skin abnormalities in Down syndrome. The low-copy and high-copy COL6A1 transgenics were born and survived in normal Mendelian proportions, without cardiac malformations or altered skin histology. These data indicate that the major promoter and enhancer sequences regulating COL6A1 expression are present in this 167-kb BAC clone. The lack of a strong cardiac or skin phenotype in the COL6A1 BAC-transgenic mice suggests that the increased expression of this gene does not, by itself, account for these phenotypes in Down syndrome.

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Acknowledgments

This work was supported by NIH grant 5P01HD035897. Tissue processing and histology was supported by a core facility of the Columbia University Comprehensive Cancer Center.

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Authors and Affiliations

  1. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, New York, New York, 10032, USA

    Luzhou Xing, Martha Salas & Benjamin Tycko

  2. Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, 10032, USA

    Luzhou Xing, Vundavalli V. Murty & Benjamin Tycko

  3. Department of Pathology, Columbia University Medical Center, New York, New York, 10032, USA

    Shivakumar Subramaniyam, Vundavalli V. Murty & Benjamin Tycko

  4. Department of Ophthamology, Columbia University Medical Center, New York, New York, 10032, USA

    Chyuan-Sheng Lin

  5. Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, New York, New York, 10314, USA

    Warren Zigman

  6. Department of Behavioral Psychology, Kennedy Krieger Institute, Baltimore, Maryland, 21205, USA

    Wayne Silverman

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  1. Luzhou Xing
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  2. Martha Salas
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  3. Chyuan-Sheng Lin
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  6. Shivakumar Subramaniyam
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  7. Vundavalli V. Murty
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  8. Benjamin Tycko
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Correspondence to Benjamin Tycko.

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Xing, L., Salas, M., Lin, CS. et al. Faithful tissue-specific expression of the human chromosome 21-linked COL6A1 gene in BAC-transgenic mice. Mamm Genome 18, 113–122 (2007). https://doi.org/10.1007/s00335-006-0082-y

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  • DOI: https://doi.org/10.1007/s00335-006-0082-y

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