Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1)

Luzhou Xing, Martha Salas, Hong Zhang, Julia Gittler, Thomas Ludwig, Chyuan Sheng Lin, Vundavalli V. Murty, Wayne Silverman, Ottavio Arancio, Benjamin Tycko

Research output: Contribution to journalArticle

Abstract

The chromosome 21 gene RCAN1, encoding a modulator of the calcineurin (CaN) phosphatase, is a candidate gene for contributing to cognitive disability in people with Down syndrome (DS; trisomy 21). To develop a physiologically relevant model for studying the biochemistry of RCAN1 and its contribution to DS, we generated bacterial artificial chromosome-transgenic (BAC-Tg) mouse lines containing the human RCAN1 gene with a C-terminal HA-FLAG epitope tag incorporated by recombineering. The BAC-Tg was expressed at levels only moderately higher than the native Rcan1 gene: approximately 1.5-fold in RCAN1BAC- Tg1 and twofold in RCAN1BAC-Tg2. Affinity purification of the RCAN1 protein complex from brains of these mice revealed a core complex of RCAN1 with CaN, glycogen synthase kinase 3-beta (Gsk3b), and calmodulin, with substoichiometric components, including LOC73419. The BAC-Tg mice are fully viable, but long-term synaptic potentiationisimpaired in proportion to BAC-Tg dosage in hippocampal brain slices from these mice. RCAN1 can act as a tumor suppressor in some systems, but we found that the RCAN1 BAC-Tg did not reduce mammary cancer growth when present at a low copy number in Tp53;WAP-Cre mice. This work establishes a useful mouse model for investigating the biochemistry and dose-dependent functions of the RCAN1 protein in vivo.

Original languageEnglish (US)
Pages (from-to)30-43
Number of pages14
JournalMammalian Genome
Volume24
Issue number1-2
DOIs
StatePublished - Feb 1 2013

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1)'. Together they form a unique fingerprint.

  • Cite this

    Xing, L., Salas, M., Zhang, H., Gittler, J., Ludwig, T., Lin, C. S., Murty, V. V., Silverman, W., Arancio, O., & Tycko, B. (2013). Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1). Mammalian Genome, 24(1-2), 30-43. https://doi.org/10.1007/s00335-012-9436-9