Abstract
Mice (Mus musculus) are the most commonly used laboratory animals. Viral metagenomics on tissues of immunodeficient mice revealed sequences of a novel mammalian astrovirus. Using PCR, we screened mice from 4 breeders, 4 pharmaceutical companies, 14 research institutes and 30 universities in the US and Japan. Mice from one US breeder tested positive while none from Japanese breeders were positive for MuAstV. Mice in over half of the universities (19/30), institutes (7/14) and pharmaceutical animal facilities (2/4) investigated revealed the presence of MuAstV. Nine mice strains tested positive including both immunodeficient strains (NSG, NOD-SCID, NSG-3GS, C57BL6-Timp-3 −/−, and uPA-NOG) and immunocompetent strains (B6J, ICR, Bash2, BALB/c). Our data indicates that MuAstV has a wide geographical, institutional and host strain distribution. Comparison of the MuAstV RdRp sequences showed numerous mutations indicating ongoing viral divergence in different facilities. This study demonstrates the need for metagenomic screening of laboratory animals to identify adventitious infections that may affect experimental outcomes.
Highlights
Mice play a significant role in biomedical research and are used to study basic biological mechanisms, model diseases and test new therapies [1,2,3]
Viral metagenomic was performed on pooled tissues from two NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) immunodeficient mice approximately five weeks old
A subsequent search with an updated GenBank database (Sep 2012) revealed the sequences were closely related to the murine astrovirus (MuAstV) reported by two groups in late 2012 [24,37]
Summary
Mice play a significant role in biomedical research and are used to study basic biological mechanisms, model diseases and test new therapies [1,2,3]. Numerous immunocompromised laboratory mouse strains have been developed that are deficient in various components of the innate or adaptive immune response. In particular, have proven useful for creating in vivo models for the study of human disease [4,5,6,7]. Elimination of the adaptive immune response in mice allows for the engraftment of human cells and tissues [4,5,6,7]. Introduction of hematopoietic stem cells into immunodeficient mice, for example, allows for the in vivo study of their differentiation into the various components of human blood [7,8,9,10,11]. Humanized mice have aided in the development of gene therapies and cell-based therapies for hematopoietic disorders in humans [7,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]
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