Comparative Anatomy and Histology: A Mouse and Human Atlas

461 Pages·2012·299.94 MB·English

by  Piper M. Treuting

Comparative Anatomy and Histology
A Mouse and Human Atlas
Comparative Anatomy and
Histology
A Mouse and Human Atlas
Editors
Piper M. Treuting, DVM, MS, Suzanne M Dintzis, MD, PhD
Diplomate, ACVP Director, Laboratory Operations
Assistant Professor, Department of Anatomic Pathology
Director, Comparative Pathology Service
University of Washington School of Medicine
Co-Director Histology and Imaging Core
Seattle, WA, USA
Assistant Professor, Department of Comparative Medicine
University of Washington School of Medicine
Seattle, WA, USA
Associate Editors
Charles W. Frevert DVM, ScD Denny Liggitt, DVM, PhD,
Director, Histology and Imaging Core Diplomate, ACVP
Co-Director, Comparative Pathology Program
Professor and Chair
Associate Professor, Department of Comparative Medicine
Department of Comparative Medicine
University of Washington School of Medicine
University of Washington School of Medicine
Seattle, WA, USA
Seattle, WA, USA
Technical Editor
Kathleen S. Montine, PhD, ELS
Senior Principal Research Scientist
Department of Pathology
University of Washington School of Medicine
Seattle, WA, USA
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List of Contributors
Kimberly H. Allison, MD Krista Marie DuBray La Perle, DVM, PhD,
University of Washington School of Medicine Diplomate, ACVP
Seattle, WA, USA The Ohio State University
Columbus, OH, USA
Kelli L. Boyd, PhD, DVM, DACVP
Vanderbilt University Medical Center Charles W. Frevert, DVM, ScD
Nashville, TN, USA University of Washington School of Medicine
Seattle, WA, USA
Cory Brayton, DVM, Diplomate, ACLAM, ACVP
Johns Hopkins University School of Medicine Philip Fleckman, MD
Baltimore, MD, USA University of Washington School of Medicine
Seattle, WA, USA
Bernard S. Buetow, DVM, PhD, DACVP
Rochelle L. Garcia, MD
Pfizer, Incorporated
University of Washington School of Medicine
San Diego, CA, USA
Seattle, WA, USA
Brad Bolon, DVM, MS, PhD, DACVP
Catherine E. Hagan, DVM, PhD
GEMpath
University of Washington School of Medicine
Longmont, CO, USA
Seattle, WA, USA
Robert D. Cardiff, MD, PhD Jack R. Harkema, DVM, PhD, DACVP
University of California at Davis Michigan State University
Davis, CA, USA East Lansing, MI, USA
Stephan A. Carey, PhD, DVM Benjamin Hoch, MD
Michigan State University University of Washington School of Medicine
East Lansing, MI, USA Seattle, WA, USA
Sindhu Cherian, MD Christopher Jerome, B. Vet. Med, PhD
University of Washington School of Medicine Think Bone Consulting, Inc.
Seattle, WA, USA Langley, WA, USA
Suzanne M. Dintzis, MD, PhD, Diplomate, ABP C. Diana Jordan
University of Washington School of Medicine University of Washington School of Medicine
Seattle, WA, USA Seattle, WA, USA
Renee Z. Dintzis, PhD C. Dirk Keene, MD, PhD
Johns Hopkins University School of Medicine University of Washington School of Medicine
Baltimore, MD, USA Seattle, WA, USA
ix
x List of Contributors
Lloyd E. King, MD, PhD Mara H. Rendi, MD, PhD
Vanderbilt Dermatology Clinic School of Medicine University of Washington School of Medicine
Nashville, TN, USA Seattle, WA, USA
Sue Knoblaugh, DVM, Diplomate, ACVP Arlin B. Rogers, DVM, PhD
Fred Hutchinson Cancer Research Center University of North Carolina
Seattle, WA, USA Chapel Hill, NC, USA
Manu M. Sebastian, DVM, PhD, DACVP
Jolanta Kowalewska, MD, PhD
Columbia University Medical Center
Medical University of Bialystok
New York, NY, USA
Bialystok, Poland
Carlos Jose Suarez, MD
Michael A. Laflamme, MD, PhD
University of Washington School of Medicine
University of Washington School of Medicine
Seattle, WA, USA
Seattle, WA, USA
John P. Sundberg, DVM, PhD
Denny Liggitt, DVM, PhD, Diplomate, ACVP
The Jackson Laboratory
University of Washington School of Medicine Bar Harbor, ME, USA
Seattle, WA, USA
Piper M. Treuting, DVM, MS, Diplomate, ACVP
Michael Linden, MD, PhD University of Washington School of Medicine
University of Minnesota Seattle, WA, USA
Minneapolis, MN, USA
Lawrence True, MD
Kathleen S. Montine, PhD, ELS University of Washington School of Medicine
University of Washington School of Medicine Seattle, WA, USA
Seattle, WA, USA
Daniel C. Tu, MD
Thomas H. Morton, Jr., DDS, MSD Casey Eye Institute
Portland, OR, USA
University of Washington School of Dentistry
Seattle, WA, USA
Mark A. Valasek, MD, PhD
University of Washington School of Medicine
Atis Muehlenbachs, MD, PhD
Seattle, WA, USA
University of Washington School of Medicine
Seattle, WA, USA
James G. Wagner, PhD
Michigan State University
Lillian B. Nanney, PhD
East Lansing, MI, USA
Vanderbilt School of Medicine
Nashville, TN, USA
Jerrold M. Ward, DVM, PhD
Global VetPathology
Isabella Phan, MD Montgomery Village, MD, USA
University of California, San Francisco
San Francisco, CA, USA
Rachel Wong, PhD
University of Washington School of Medicine
Julie Randolph-Habecker, PhD Seattle, WA, USA
Fred Hutchinson Cancer Research Center
Seattle, WA, USA
Steve Rath, PA (ASCP), MHS
University of Washington School of Medicine
Seattle, WA, USA
Acknowledgments
An atlas of this scope does not come together the expert technical staff of the University of
without the committed talents of many people. Washington (UW) Histology and Imaging Core—
In addition to thanking the expert authors and Kerrie Allen and Brian Johnson—along with
assistant editors, we (the co-editors in chief) wish student helpers Cara Appel and Kelsie Ovenell.
to thank the many people whose time, effort, and We wish to acknowledge and thank S. Chou who
encouragement helped us to complete this work. provided encouragement for and gave form to the
We humbly recognize that we may inadvertently cover art concept. She also provided a portion of
miss some that are deserving of a personal thank- the final cover drawing and the Chapter 1 figures.
you. To all who participated in this work, we are Sara Samuelson, S. S. Illustrations (sarasamuelson.
thankful for you and your contributions. We hope com), provided the drawings for Chapter 20,
that the final product serves as a proper thank-you including the unique rendition of the sensory and
for a job well done. motor musculi.
Gross and microscopic images are the mainstay The successful completion of this work would not
of this text, and obtaining publication quality have been possible without the collegial support
images to compare mouse and human tissues of our Department Chairs: Denny Liggitt, Nelson
was a formidable challenge. Production of the Fausto, and Tom Montine. Major contributions
mouse anatomic images began with skilled and were also provided by faculty, residents, and
detailed anatomic dissections performed in part students in the UW Departments of Comparative
by Sue Knoblaugh. Expert macro photography Medicine and Pathology, and by our patient
was provided by Gavin W. Sisk. We wish to warmly editors at Elsevier, Mara Conner and Megan
thank Sue and Gavin for their efforts and good- Wickline. Special recognition is reserved for Kathy
natured understanding of the need to get “The Montine, our UW technical editor, who organized
Perfect Dissection and Shot” and tolerance of the chapters and coordinated the submissions.
our “assistance” with their efforts. We are pleased Her contribution is immeasurable both for
to present the mouse anatomical preparations the timely completion of this work and for our
rendered, by Dragonfly Media Group, in the collective mental health.
style of medical illustrator Frank H. Netter, MD.
We thank the Netter family and Elsevier for Throughout this process, we have learned to
providing access to Netterimages.com the Netter float with the ebb and flow of the writing and
color palette, and for great patience when working editing process, pulling authors along with us and
with one of us (PT) in editing the final mouse occasionally even stalking them in order to make
images. their unpaid labor a top priority—only to then
edit their carefully chosen words.
To obtain mouse microscopic images, harvested
mouse tissues were processed by Histology We suspect that most of our critical readers will be
Consultation Services (HCS) of Everson, WA pathologists and will be vociferously opinionated.
(http://histocs.com/index.html) and we thank We welcome their opining along with suggestions
LeRoy Brown, CEO, for his assistance. Tissue for improvement. We recognize that there will
and slide organization, virtual slide scanning, be errors in this Atlas for which we take full
and database management was performed by responsibility.
xi
xii Acknowledgments
To our families and the Montine family, we owe Finally, we wish to thank the mice. It is our hope
many thanks. Your understanding and support that this Atlas will allow for greater understanding
of our academic pursuits enabled this work. We of the comparative anatomy of the mouse and,
recognize the burden this placed on you, and we ultimately, refined models of human disease.
are grateful for your willingness to cheerfully step
in during our absences. Piper M. Treuting and Suzanne M. Dintzis
Seattle, WA
Introduction
1
Piper M. Treuting, Suzanne M. Dintzis, and Kathleen S. Montine
University of Washington School of Medicine, Seattle, WA, USA
Overview hypothesis-driven research. Mouse models of
human disease have proven valuable to biomedical
research but only with appropriate validation
This atlas is aimed at the new mouse investigator, and careful translation of mouse data to human
as well as medical and veterinary pathologists systems. Validation of mouse models as defined
who wish to expand their knowledge base into by Cardiff and colleagues involves determining
comparative anatomy and histology. It guides to what extent the attributes of the experimental
the reader through normal mouse anatomy and system (in this case, the mouse phenotype) match
histology using direct comparison to the human. the attributes of human disease. As the phenotype
The side-by-side comparison of mouse and human of the human disease or condition being modeled
tissues highlights the unique biology of the mouse, becomes more complex, the validity of the mouse
which has great impact on the validation of mouse model becomes more important. A mouse model
models of human disease. that is not appropriately validated does not value
the use of those animals, wastes research dollars,
and can even result in risks to humans if mouse
preclinical data are incorrectly translated to
Comparative human patients.
Pathology: Closing Validation of mouse models through phenotyping
(discussed in Chapter 2) and the translation of
a Gap experimental findings in mice to human disease
are best done by a comparative pathologist and
require a broad and unique skill set covering
Biomedical research institutions worldwide are mouse and human gross and histologic anatomy
literally overrun with mice. More than 60% of and pathobiology. Trained comparative
extramural National Institutes of Health (NIH)– pathologists have attended veterinary or medical
funded grants use animals; most of these are school and have further specialty training in
mouse models of human disease, many of which pathology. They must understand how a research
involve genetically engineered mice (GEM). This question may be impacted by the interplay of the
is a testament to the perceived value of mice mouse background strain, genetic manipulations,
to model the human condition and to support breeding schema, sex, housing, diet, age, and
Comparative Anatomy and Histology.
© 22001122 Elsevier Inc. All rights reserved. 1
2 Comparative Anatomy and Histology
intercurrent pathogenic or commensal organisms. in comparative pathology that will assist them in
Unfortunately, the population of formally trained planning experiments and interpreting results.
comparative pathologists is not increasing as Because formal training to become a comparative
rapidly as that of mice. In our experiences at pathologist is limited, the research community
the University of Washington, we recognize that looks to novel solutions such as online training
medical pathologists are increasingly asked to academies or annual intensive mouse pathology
interpret mouse pathologic lesions. Likewise, workshops to bring together geographically and
veterinary pathologists need to know more about culturally dispersed mouse pathology experts.
human disease because the bulk of the animals There are numerous online resources and
they care for and work with arise from funded journal articles, rodent pathology atlases, rodent
work on human disease. In addition, many new or laboratory animal pathology mini-courses,
mouse investigators are eager to acquire training and ever-expanding virtual communities of
TABLE 1 Representative Features and Major Differences
General Features Mouse Human
Class Mammalia Mammalia
Order Rodentia Primata
Family Muridae Hominidae
Genus and species Mus musculus Homo sapiens
Sexual maturity 5–6 weeks 10–15 years
Adult body weight (female) 18–35 g 75 kg
Adult body weight (male) 20–40 g 87 kg
Surface area 0.03–0.06 cm2 1.6–1.9 m2
Life span 1–3 years Average 67 years
Maximum life span reported 4 years 122 years
No. of offspring 5–11, strain-dependent 1–2
Young Altricial Same
Legs 4 2
Arms 0 2
Nails Yes Yes
Tail Yes None or poorly developed
Vertebral formula C7 T13 L6 S4 Cd28 C7 T12 L5 S5 Cd4
Integument Haired skin predominates Glabrous skin predominates
Sweat glands Eccrine only, restricted to feet Apocrine and eccrine
Vibrissae Yes No
Mammary glands 10 diffuse; cervical, thoracic, abdominal, inguinal 2 discrete, pectoral
Male nipples No Yes
Exorbital lacrimal glands Yes No
Harderian glands Yes No
Lung lobes 4 right, 1 left 3 right, 2 left
Cerebral gyri and sulci No Yes
Liver lobes 4: right, left, median, caudate 4: right, left, caudate, quadrate
Nonglandular forestomach Yes No
Pancreas Relatively diffuse in mesentery, indistinct lobation Well-demarcated, left and right lobes,
connected by body
Seminal vesicles Yes, very prominent Yes
Prostate Yes, 6 lobes Yes, 4 lobes
Bulbourethral gland Yes Yes
Coagulating gland Yes No
Preputial gland Yes No
Clitoral gland Yes No
Uterus Bicornate Simplex
Placenta Discoid, labyrinth, hemotrichorial Discoid, villious, hemochorial
Tonsils No Yes
Gut-associated lymphoid tissue Yes Yes
Nasal-associated lymphoid tissue Yes No
Bronchus-associated lymphoid tissue Variable Yes
Zymbal gland Yes No, smaller sebaceous glands in
external acoustic meatus
Os clitoris Yes No
Os penis Yes No
Vomerulonasal organ Yes Controversial
Chapter 1 Introduction 3
comparative pathologists that in concert serve to translational research settings. To observe and
train individuals interested in expanding their measure deviants, normal must be well understood.
mouse pathology skills. Only then can phenotypic differences in the vast
array of human disease models be understood
To this growing body of knowledge, we are pleased and appreciated. We hope this reference will
to contribute a resource that is currently not help improve communication between veterinary
available—a side-by-side comparison of normal and medical pathologists, and among mouse
mouse and human tissue that will highlight the investigators, regarding normative structures.
unique biology of the mouse, which has great Pathology of disease, in which the debate
impact on the histopathology. Although most regarding terminology is even more complex, is
tissue at the level of the light microscope is similar not within the scope of this atlas. Together with the
between Mus musculus and Homo sapiens, there are educational resources noted previously, this atlas
critical differences (Tables 1 and 2; Figures 1 and provides practical information to improve technical
2), and in order to understand differences arising proficiency in basic comparative mouse anatomy
from various models, normal must be recognized. and histology. Perhaps just as importantly, we hope
This atlas will establish a reliable baseline to this atlas will provide insight into when enlisting
fill a gap in mouse phenotypic evaluation in the aid of an expert is prudent.
TABLE 2 Directional Anatomy Terms
Direction Mouse Human
Toward the head Cranial, craniad Cranial (axial skeleton)
Toward the nose Rostral (on head), cranial (on rest of body) Anterior
Toward the tail Caudal, caudad Caudal (axial skeleton)a
Toward the abdomen Ventral, ventrad Anterior
Toward the feet Distal Distal (appendicular skeleton)a
Toward the trunk Proximal Same
Toward the spine Dorsal, dorsad Caudal
Toward the palms or soles Palmar (front), plantar (rear) Same
Away from the palms or soles Dorsal Same
aHuman anatomy differs if one is speaking of the axial or appendicular skeleton.