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X-Ray Annotation Mouse Atlas This Publication Is Under a Creative Commons License J. Ruberte – A. Carretero – H. Cater G. Gràcia – C. Lally X-Ray Annotation Mouse Atlas This publication is under a Creative Commons license. Total or partial reproduction and public communication is permitted, as long the authorship is acknowledged. Changes of the original publication, its commercial use, and creation of derivative works is not allowed. ILLUSTRATIONS: Helena Ariño. 08208, Sabadell, Spain. The information and views set out in this publication are those of the authors and do not necessarily reflect the official opinion of the European Union. Neither the European Union institutions and bodies nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein. AUTHORS Prof. Dr. Jesús Ruberte (DVM, PhD) Head of the Mouse Imaging Platform. Center for Animal Biotechnology and Gene Therapy. Department of Animal Health and Anatomy. Veterinary School. Universitat Autònoma de Barcelona, Spain. Prof. Dr. Ana Carretero (DVM, PhD) Mouse Imaging Platform. Center for Animal Biotechnology and Gene Therapy. Department of Animal Health and Anatomy. Veterinary School. Universitat Autònoma de Barcelona, Spain. Dr. Heather Cater (BSc, PhD) Phenotyping Manager. Medical Research Council. Harwell, Oxfordshire, United Kingdom. Dr. Guillem Gràcia (DVM) Center for Animal Biotechnology and Gene Therapy. Department of Animal Health and Anatomy. Veterinary School. Universitat Autònoma de Barcelona, Spain. Mr. Connor Lally (BSc, MSc) Senior Phenotyper and Data manager. Medical Research Council. Harwell, Oxfordshire, United Kingdom. FOREWORD One of the biggest challenges facing the biomedical sciences and medicine is the dark genome. Much of the human genome is unexplored and there remain thousands of genes for which we have little or no knowledge of function and their impact on disease. This is a very serious impediment to the development of a comprehensive understanding of the genetic bases of disease and progress in genomic medicine. If we are to make significant progress with understanding the mechanisms and pathological bases of disease, and develop and implement appropriate therapies, we need to address this challenge, which pervades all progress in the biomedical sciences. The mouse remains the key genetic tool for exploring the dark genome. The mouse genetics community, including the International Mouse Phenotyping Consortium (IMPC), is focused on the generation of a library of mouse mutants for every orthologous human gene. The phenotyping of each of these mutants will provide a comprehensive catalogue of mammalian gene function. Importantly, such efforts can be done at scale, ensuring that every gene is analysed and that the dark genome is illuminated. Already, many genes for which hitherto we had no information about function have emerged from the darkness, providing fascinating insight into their potential role in disease. Across many disease areas an extensive, unexplored landscape of novel gene function has been uncovered. The success of this endeavour depends upon the development of efficient and standardised phenotyping tools and approaches. The phenotyping platforms that are applied to the analysis of mutants must deliver robust and reproducible data and thus the development of standardised tools is critical. The X-ray Annotation Mouse Atlas is a major new advance in mouse phenotyping providing a comprehensive and standardised atlas of bone morphology and architecture. It provides a fundamental and vital tool which will speed and improve the characterisation and annotation of mouse mutants. The authors are to be congratulated on this new and powerful atlas which is already contributing to our understanding of bone pathology and disease mechanisms. Steve Brown February 2021 PREFACE Mice represent over 60% of laboratory skeleton can be observed and learned to animals used in Europe for phar- identify using this publication. Following maceutical and biotechnology compa- the IMPC standard operating procedures nies, as well as research institutions. The (https://www.mousephenotype.org/impre transgenic and genetic manipulation ss), dorso-ventral and latero-lateral radio- technologies applied to the mouse have graphies from 14 weeks old male and provided experimental proof that a female C57BL/6N mice were performed significant proportion of inherited disea- using a Ultrafocus DXA and a Faxitron ses share a common genomic source. MX-20 (Hologic®, Marlborough, Massa- The recent revolution in gene editing, the chusetts, USA). Isolated bone radiogra- CRISPR-Cas9 technology, has also pro- phies were obtained after digestion of vided an additional and powerful ap- soft tissues using pancreatin solution proach to design and produce mouse (0.05%). models with the same insertion or de- Special attention has been paid to letion missense mutations that occur in presenting the radiological anatomy of the human genome and are responsible the head, the carpus, the tarsus, and the for a significant proportion of inherited or vertebral column. To better understand acquired human disease. the complex anatomy of the skull, x-rays This success for testing molecular di- of its isolated bones are presented sease hypotheses in mice has encou- showing their shape, processes, fora- raged the development of massive global mina, etc. In addition, the boundaries of mouse projects, such as the International each bone are delimited on the X-ray Mouse Phenotyping Consortium (IMPC), images of the complete skull. Anatomical which is building a catalogue of mam- variations in the number and fusion of malian gene function by producing and carpal and tarsal bones have been phenotyping a knockout mouse line for studied in a total of 14 Individuals. The every protein-coding gene. To date, the frequency of appearance for each ana- IMPC has generated and characterised tomical variation is indicated in percen- 7,626 mutant lines creating 246,749 X- tage. Vertebral regions have been pre- ray images that need to be analyzed and sented showing their vertebrae isolated understood. and drawing interpretative schemes to understand how anatomical structures Anatomy is the bedrock on which belonging to two contiguous vertebrae radiology has been based. However, to overlap in the same radiographic loca- our knowledge there is currently not a tion. Finally, the most important bone specific publication devoted to the mouse gender differences have also been de- radiological skeletal anatomy. Such a monstrated comparing male and female publication would help to diagnose ap- littermates. Male bones in general are propriately the huge number of X-ray bigger that their corresponding female images produced by the international specimens. consortia. For these reasons, here we introduce a complete description of mou- Muscular processes are more prominent se skeletal radiology using a set of 152 in males and the shape of articular X-ray images, 16 original drawings, and surfaces presented slight differences 590 anatomical references. All the im- when comparing sexes. Interestingly, as portant anatomical details of the mouse happen in other mammals including man, PREFACE the morphology of the pelvis is different “Anatomisches Bildwörterbuch der inter- between male and female mice. antionalen Nomenklatur” (3rd edition, 1993), by H. Feneis. We have also taken The anatomical terms that have been into consideration the mouse anatomical used here to describe the morphology of ontologies displayed in the eMouse Atlas the mouse skeleton mainly correspond to Project (EMAP). This publication has long the “Nomina Anatomica Veterinaria (NAV)” been demanded by the technicians in (4th edition, 1992). charge of analyzing the bone radiographs However, there are bones that exist in the obtained in “mouse clinics” worldwide. mouse, the clavicle for example, which is Today, thanks to the collaboration very similar to humans, and not very between the Universitat Autònoma de common in domestic animals. In these Barcelona and the Mary Lyon Centre situations, we have used the human (MRC Harwell Institute) it is a pleasure to anatomical nomenclature published in the present it to the mouse community. TABLE OF CONTENTS 1. Dorso-ventral mouse radiography . 1 2. Latero-lateral mouse radiography . 2 3. Skull . 3 4. Mandible . 15 5. Cervical vertebrae . 16 6. Thoracic vertebrae . 19 7. Ribs . 21 8. Sternum . 22 9. Lumbar vertebrae . 23 10. Sacrum . 25 11. Caudal vertebrae . 27 12. Skeleton of the forelimb . 28 13. Skeleton of the hindlimb . 34 14. Gender differences . 41 15. Bibliography . 46 16. Index . 48 1 Dorso-ventral mouse radiography A B 6 1 1 4 3 5 2 7 8 10 9 11 12 13 A) Dorsal view from a BL6/SJL mouse. B) Dorso-ventral radiography. 1: Cranium; 2: Scapula; 3: Humerus; 4: Radius; 5: Ulna; 6: Forepaw; 7: Ribs; 8: Vertebral column; 9: Hip bone; 10: Femur; 11: Tibia; 12: Fibula; 13: Hindpaw. 2 Latero-lateral mouse radiography A B 6 7 5 8 16 4 9 2 11 17 1 3 12 10 13 14 18 19 15 20 A) Left lateral view from a BL6/SJL mouse. B) Latero-lateral radiography. 1: Facies; 2: Cranium; 3: Mandible; 4: Cervical vertebrae; 5: Thoracic vertebrae; 6: Lumbar vertebrae; 7: Sacrum; 8: Caudal vertebrae; 9: Ribs; 10: Sternum; 11: Scapula; 12: Humerus; 13: Radius; 14: Ulna; 15: Forepaw; 16: Hip bone; 17: Femur; 18: Tibia; 19: Fibula; 20: Hindpaw. 3 Skull A 4 4 5 5 3 3 10 10 2 B 4 4 C 5 5 10 1 8 8 3 7 13 7 3 6 6 10 10 9 9 2 11 11 12 12 A) Skeleton of the head. Dorso-ventral radiography. B) Skull. Dorso-ventral radiography. C) Mandibles. Dorso-ventral radiography. 1: Viscerocranium (facial bones); 2: Neurocranium; 3: Mandible; 4: Upper incisor tooth; 5: Lower incisor tooth; 6: Upper molar teeth; 7: Lower molar teeth; 8: Body of mandible; 9: Ramus of mandible; 10: Coronoid process; 11: Condyloid process; 12: Angular process; 13: Intermandibular joint. 4 Skull B 3 3 4 4 A 1 1 1 1 5 2 2 12 9 9 13 6 6 9 9 8 8 11 11 2 2 7 7 13 10 10 14 14 A) Position of nasal and frontal bones.
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