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Diener, S. ; Bayer, S. ; Sabrautzki, S. ; Wieland, T. ; Mentrup, B.* ; Przemeck, G.K.H. ; Rathkolb, B. ; Graf, E. ; Hans, W. ; Fuchs, H. ; Horsch, M. ; Schwarzmayr, T. ; Wolf, E.* ; Klopocki, E.* ; Jakob, F.* ; Strom, T.M. ; Hrabě de Angelis, M. ; Lorenz-Depiereux, B.

Exome sequencing identifies a nonsense mutation in Fam46a associated with bone abnormalities in a new mouse model for skeletal dysplasia.

Mamm. Genome 27, 111-121 (2016)
Postprint DOI PMC
Open Access Green
We performed exome sequencing for mutation discovery of an ENU (N-ethyl-N-nitrosourea)-derived mouse model characterized by significant elevated plasma alkaline phosphatase (ALP) activities in female and male mutant mice, originally named BAP014 (bone screen alkaline phosphatase #14). We identified a novel loss-of-function mutation within the Fam46a (family with sequence similarity 46, member A) gene (NM_001160378.1:c.469G>T, NP_001153850.1:p.Glu157*). Heterozygous mice of this mouse line (renamed Fam46a (E157*Mhda)) had significantly high ALP activities and apparently no other differences in morphology compared to wild-type mice. In contrast, homozygous Fam46a (E157*Mhda) mice showed severe morphological and skeletal abnormalities including short stature along with limb, rib, pelvis, and skull deformities with minimal trabecular bone and reduced cortical bone thickness in long bones. ALP activities of homozygous mutants were almost two-fold higher than in heterozygous mice. Fam46a is weakly expressed in most adult and embryonic tissues with a strong expression in mineralized tissues as calvaria and femur. The FAM46A protein is computationally predicted as a new member of the superfamily of nucleotidyltransferase fold proteins, but little is known about its function. Fam46a (E157*Mhda) mice are the first mouse model for a mutation within the Fam46a gene.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Gene; Families; Susceptibility; Classification; Pathway; Disease; Beta; Mice
ISSN (print) / ISBN 0938-8990
e-ISSN 1432-1777
Journal Mammalian Genome
Quellenangaben Volume: 27, Issue: 3-4, Pages: 111-121 Article Number: , Supplement: ,
Publisher Springer
Publishing Place New York
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Experimental Genetics (IEG)
German Center for Diabetes Reseach (DZD)
CF Comparative Medicine (CF-Comparative Medicine)