The first Scube3 mutant mouse line with pleiotropic phenotypic alterations

Helmut Fuchs, Sibylle Sabrautzki, Gerhard K.H. Przemeck, Stefanie Leuchtenberger, Bettina Lorenz-Depiereux, Lore Becker, Birgit Rathkolb, Marion Horsch, Lillian Garrett, Manuela A. Östereicher, Wolfgang Hans, Koichiro Abe, Nobuho Sagawa, Jan Rozman, Ingrid L. Vargas-Panesso, Michael Sandholzer, Thomas S. Lisse, Thure Adler, Juan Antonio Aguilar-Pimentel, Julia Calzada-WackNicole Ehrhard, Ralf Elvert, Christine Gau, Sabine M. Hölter, Katja Micklich, Kristin Moreth, Cornelia Prehn, Oliver Puk, Ildiko Racz, Claudia Stoeger, Alexandra Vernaleken, Dian Michel, Susanne Diener, Thomas Wieland, Jerzy Adamski, Raffi Bekeredjian, Dirk H. Busch, John Favor, Jochen Graw, Martin Klingenspor, Christoph Lengger, Holger Maier, Frauke Neff, Markus Ollert, Tobias Stoeger, Ali önder Yildirim, Tim M. Strom, Andreas Zimmer, Eckhard Wolf, Wolfgang Wurst, Thomas Klopstock, Johannes Beckers, Valerie Gailus-Durner, Martin Hrabé de Angelis

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein) family consists of three independent members, Scube1-3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3N294K/N294K), which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the GermanMouse Clinic (GMC). Scube3N294K/N294K mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB), associated with the chromosomal region of human SCUBE3. In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3N294K/N294K mice. The Scube3N294K/N294K mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function.

Original languageEnglish (US)
Pages (from-to)4035-4046
Number of pages12
JournalG3: Genes, Genomes, Genetics
Volume6
Issue number12
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Mouse model
  • Paget disease of bone (PDB)
  • Pleitropy
  • SCUBE3
  • Systemic phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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