The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.
Helmut FuchsSibylle SabrautzkiGerhard K H PrzemeckBettina Lorenz-DepiereuxLore BeckerBirgit RathkolbMarion HorschLillian GarrettManuela A ÖstereicherWolfgang HansKoichiro AbeNobuho SagawaJan RozmanIngrid L Vargas-PanessoMichael SandholzerThomas S LisseThure AdlerJuan Antonio Aguilar-PimentelJulia Calzada-WackNicole EhrhardRalf ElvertChristine GauSabine Maria HölterKatja MicklichKristin MorethCornelia PrehnOliver PukIldiko RaczClaudia StoegerAlexandra VernalekenDian MichelSusanne DienerThomas WielandJerzy AdamskiRaffi BekeredjianDirk H BuschJohn FavorJochen GrawMartin KlingensporChristoph LenggerHolger MaierFrauke NeffMarkus OllertTobias StoegerAli Oender YildirimTim M StromAndreas ZimmerEckhard WolfWolfgang WurstFlorentine RadelfahrJohannes BeckersValerie Gailus-DurnerMartin Hrabě de AngelisPublished in: G3 (Bethesda, Md.) (2016)
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 German Mouse 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.