The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.
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/N294Kmutants 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/N294Kmice. The Scube3N294K/N294Kmutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.
Helmut
0000-0002-5143-2677
H
Fuchs
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Research Unit Comparative Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Sibylle
0000-0002-3435-921X
S
Sabrautzki
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.
Gerhard K H
0000-0003-3730-3454
GK
Przemeck
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Stefanie
0000-0003-3730-3454
S
Leuchtenberger
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Bettina
B
Lorenz-Depiereux
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Lore
0000-0002-6890-4984
L
Becker
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.|Molecular Animal Breeding and Biotechnology, Gene Center of the Ludwig-Maximilians-Universität München, 81377, Germany.
Birgit
0000-0003-1239-0547
B
Rathkolb
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Marion
M
Horsch
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Lillian
L
Garrett
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Manuela A
0000-0003-4333-2366
MA
Östereicher
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Wolfgang
0000-0002-1221-4108
W
Hans
Department of Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
Koichiro
K
Abe
Department of Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
Nobuho
N
Sagawa
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.
Jan
0000-0002-8035-8904
J
Rozman
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, 80336, Germany.|German Center for Vertigo and Balance Disorders, Munich, 81377 Germany.
Ingrid L
0000-0001-5682-8454
IL
Vargas-Panesso
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Michael
M
Sandholzer
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Thomas S
TS
Lisse
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Thure
0000-0001-5434-9521
T
Adler
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Juan Antonio
0000-0002-4694-7107
JA
Aguilar-Pimentel
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Julia
J
Calzada-Wack
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Cedars-Sinai Medical Genetics Research Institute, Los Angeles, California 90048.
Nicole
N
Ehrhard
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Ralf
R
Elvert
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Christine
0000-0002-4262-3071
C
Gau
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Sabine M
0000-0003-4878-5241
SM
Hölter
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Molecular Animal Breeding and Biotechnology, Gene Center of the Ludwig-Maximilians-Universität München, 81377, Germany.
Katja
K
Micklich
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Kristin
0000-0001-7170-5284
K
Moreth
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Cornelia
0000-0002-1274-4715
C
Prehn
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Oliver
0000-0002-4302-6513
O
Puk
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127, Germany.
Ildiko
0000-0001-7329-0641
I
Racz
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Claudia
0000-0001-8361-0274
C
Stoeger
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, 80336, Germany.|German Center for Vertigo and Balance Disorders, Munich, 81377 Germany.
Alexandra
A
Vernaleken
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Dian
D
Michel
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Susanne
S
Diener
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Thomas
T
Wieland
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.
Jerzy
0000-0001-9259-0199
J
Adamski
Division of Cardiology, University of Heidelberg, 69120, Germany.
Raffi
R
Bekeredjian
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675, Germany.
Dirk H
0000-0001-8713-093X
DH
Busch
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
John
J
Favor
Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Jochen
0000-0003-0298-9660
J
Graw
Else Kröner Fresenius Center for Nutritional Medicine, Technische Universität München, 85350 Freising-Weihenstephan, Germany.|ZIEL - Institute for Food and Health, Technische Universität München, 85350 Freising-Weihenstephan, Germany.
Martin
0000-0002-4502-6664
M
Klingenspor
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Christoph
0000-0002-2207-4153
C
Lengger
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Holger
0000-0003-2514-8290
H
Maier
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Frauke
F
Neff
Department of Dermatology and Allergy, Biederstein, Klinikum Rechts der Isar, Technische Universität München, 80802, Germany.|Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354 Luxembourg.|Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, DK-5000 Denmark.
Markus
M
Ollert
Institute of Lung Biology and Diseases Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Tobias
0000-0002-2790-0389
T
Stoeger
Institute of Lung Biology and Diseases Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Ali Önder
0000-0003-1969-480X
AÖ
Yildirim
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Tim M
TM
Strom
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127, Germany.
Andreas
0000-0003-3127-287X
A
Zimmer
Molecular Animal Breeding and Biotechnology, Gene Center of the Ludwig-Maximilians-Universität München, 81377, Germany.
Eckhard
0000-0002-0430-9510
E
Wolf
Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Neurodegenerative Diseases, 80336 Munich, Germany.|Lehrstuhl für Entwicklungsgenetik, Technical University München-Weihenstephan, c/o Helmholtz Zentrum München, 85764 Neuherberg, Germany.|Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, 80336, Germany.
Wolfgang
W
Wurst
Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, 80336, Germany.|German Center for Vertigo and Balance Disorders, Munich, 81377 Germany.|German Center for Neurodegenerative Diseases, 80336 Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, 80336, Germany.
Thomas
0000-0003-2805-4652
T
Klopstock
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München, 85350 Freising-Weihenstephan, Germany.
Johannes
0000-0001-7874-3822
J
Beckers
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.|German Center for Diabetes Research, 85764 Neuherberg, Germany.
Valerie
V
Gailus-Durner
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany hrabe@helmholtz-muenchen.de.|German Center for Diabetes Research, 85764 Neuherberg, Germany.|German Center for Vertigo and Balance Disorders, Munich, 81377 Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München, 85350 Freising-Weihenstephan, Germany.
Martin
0000-0002-7898-2353
M
Hrabé de Angelis
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006023:Glycoproteins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010001:Osteitis Deformans / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012863:Skeleton / Q000002:abnormalities
D002135:Calcium-Binding Proteins; D006023:Glycoproteins; C493801:Scube3 protein, mouse
Paget disease of bone (PDB); SCUBE3; mouse model; pleitropy; systemic phenotype