The occurrence of tarsal injuries in male mice of C57BL/6N substrains in multiple international mouse facilities.

Eleanor Herbert,Cheryl L Scudamore,Colin Mckerlie,Jean-Paul Wiegand,Ann M Flenniken,Sara Wells,Dawei Qu,Marie Hutchison,Jacqueline K White,Brenda Kick,Liane Hobson,Michelle Stewart,Lauryl M J Nutter,Juan Antonio Aguilar-Pimentel,Martin Hrabě De Angelis ,Bonnie L Lyons ,Rosalinda Doty,Mary E Dickinson ,John R Seavitt

doi:10.1371/journal.pone.0230162

Abstract

Dislocation in hindlimb tarsals are being observed at a low, but persistent frequency in group-housed adult male mice from C57BL/6N substrains. Clinical signs included a sudden onset of mild to severe unilateral or bilateral tarsal abduction, swelling, abnormal hindlimb morphology and lameness. Contraction of digits and gait abnormalities were noted in multiple cases. Radiographical and histological examination revealed caudal dislocation of the calcaneus and partial dislocation of the calcaneoquartal (calcaneus-tarsal bone IV) joint. The detection, frequency, and cause of this pathology in five large mouse production and phenotyping centres (MRC Harwell, UK; The Jackson Laboratory, USA; The Centre for Phenogenomics, Canada; German Mouse Clinic, Germany; Baylor College of Medicine, USA) are discussed.

Highlights

Inbred strains of laboratory mice are used to standardise the genetic background of mutant mouse strains to reduce data variability
Mice were examined for tarsal injury at five mouse phenotyping centres: MRC Harwell: Animal studies are performed in compliance with guidelines issued by the Medical Research Council (MRC) (UK) in “Responsibility in the Use of Animals for Medical Research” (July 1993)
Affected tarsi showed a loss of the abrupt right angle formed from the calcaneus and the calcaneal tendon, and there was variable soft tissue swelling sometimes accompanied with redness (Fig 1)

Summary

Introduction

Inbred strains of laboratory mice are used to standardise the genetic background of mutant mouse strains to reduce data variability. Produced by >20 consecutive generations of sibling mating, the controlled homogeneity of inbred strains such as C57BL/6N is accompanied by the fixing of spontaneous mutations in inbred genomes. Many monogenic mutations have been identified in inbred mouse strains, including those causing retinal degeneration in C3H strains [1] and age-related deafness in C57BL/6 strains [2]. The characterisation of these mutations has allowed their impact on individual research programs to be assessed and alternative genetic backgrounds used if they interfered with the primary purpose of the studies.

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Conclusion