Nonhuman primate models for human diseases

210 Pages·1983·5.58 MB·English

by  Dukelow, W. Richard

Nonhuman
Primate Models
for
Human Diseases
Editor
W. Richard Dukelow, Ph.D.
Professor and Director
Endocrine Research Unit
Michigan State University
East Lansing, Michigan
Boca Raton London New York
CRC Press, Inc.
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Taylor & BFroanccais GRroautpo, nan, iFnfloormriad bau siness
First published 1983 by CRC Press
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Library of Congress Cataloging-in-Publication Data
Main entry under title:
Nonhuman primate models for human diseases.
Bibliography: p.
Includes index.
1. Diseases—Animal models. 2. Primates—
Diseases. 3. Primates—Physiology.
I. Dukelow, W. Richard.
RB125.N66 1983 619’.98 82-4519
ISBN 0-8493-6466-3 AACR2
A Library of Congress record exists under LC control number: 82004519
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PREFACE
The use of nonhuman primates as laboratory animals has a relatively short history.
While colonies of rhesus monkeys existed in the early 1920s, their use was largely
restricted to reproductive and embryological studies. These colonies were of historic
importance but also, due to the state of knowledge of animal care at that time, they
suffered from excessively high incidences of tuberculosis and respiratory disease. The
turnover rate in such colonies was high and animals seldom reached advanced age where
they could have provided valuable animal models for some of the diseases encountered
by aging humans.
Today conditions have changed. Advances in all medical fields have improved the
quality of animal care in research laboratories. Improved methods of capture and trans-
port have resulted in the arrival of healthier animals and an increased knowledge of
individual species has improved their status in the laboratory.
For many years the rhesus monkey was the standard-bearer as the monkey-model for
human problems. This monkey was studied extensively and nearly every major uni-
versity or medical school maintained a colony of rhesus monkeys for research. In the
late 1950s the extensive use of this animal for the production of poliomyelitis vaccine
caused the government of India to place an embargo on the exportation of this species.
This embargo reflected that government's concern over shipping losses and the deci-
mation of the native rhesus population. In retrospect, this embargo represented a major
turning point in the use of nonhuman primates for research. The resultant shortage of
rhesus monkeys forced consideration of alternate methods of production of the animals.
Captive colonies on islands and in corrals were established to produce rhesus monkeys.
Even more important, was the trend to study other nonhuman primate species. Biolog-
ical studies of many of the 200 species of primates were undertaken and animals which
previously had merely been curiosities in zoological gardens were found to have val-
uable research uses. As in earlier years with the rhesus monkey, techniques of colony
management, nutrition, and disease prevention had to be developed for each species.
The benefits from these studies aided not only the medical researchers but also con-
tributed to methods of rearing and keeping the animals in other areas of captivity. While
the human population of the world was expanding and the lumbering interests were
pushing the nonhuman primates deeper and deeper into their native forests, an increas-
ing number of species were added to the list of endangered animals. Many species may
yet find their final locale to be in a game preserve or zoological garden.
While research has enabled us to better understand the nonhuman primates, they have
repaid that by providing medical scientists with important tools for the study of human
biomedical problems. This book is about those research tools. The book was designed
by identifying areas of human medical research that are under intensive research study
today. Authors were then selected based on their expertise at using nonhuman primates
as models for the human condition. Each was asked to use as comparative an approach
as possible, to provide the reader with knowledge relating to the usefulness of various
nonhuman primate species to each specific research area.
A final comment should be made with regard to the word "model". The ultimate
model for man must, of necessity, be man. No single species of any animal can exactly
duplicate what occurs in the human. Traditionally we have told ourselves that the closer
a species is to man on the evolutionary ladder, the more ideal that species is for com-
parative research. While true in some cases there are many reasons to argue against
this assumption. In many areas of research common laboratory or domestic animals
more nearly reflect the human problem than do nonhuman primates. Accordingly, in
many portions of this book, the dissimilarities are emphasized as well as the similarities.
It is important for the reader to recognize the possible shortcomings of a given species
as a biomedical model, as well as its advantages.
W. Richard Dukelow
East Lansing, Michigan
THE EDITOR
Dr. W. Richard Dukelow obtained his B .S., M.S., and Ph.D. at the University of
Minnesota, Minneapolis, and completed his postdoctoral studies at the University of
Georgia, Athens, and the Oregon Regional Primate Research Center, Beaverton. He
served as Assistant Professor of Biochemistry at the University of Georgia and is pres-
ently Professor of Physiology and Animal Science, and Director of the Endocrine Re-
search Unit, at Michigan State University, East Lansing.
Dr. Dukelow was a recipient of an N.I.H. Research Career Development Award in
1970 and is a research specialist in reproductive physiology and biochemistry. He was
a member of the organizing committee of the American Society of Primatologists and
has served as Treasurer of that organization since its inception. He is the author of over
150 scientific publications, most relating to the reproduction of nonhuman primates.
He is also author of the book, Graduate Student Survival, published in 1980 (Charles
C Thomas).
CONTRIBUTORS
Irwin S. Bernstein, Ph.D. Ronald D. Hunt, D.V.M.
Professor of Psychology Professor of Comparative Pathology
Department of Psychology Director
University of Georgia New England Regional Primate
Athens, Georgia Research Center
Research Professor Harvard Medical School
Yerkes Regional Primate Research Southborough, Massachusetts
Center of Emory University
Lawrenceville, Georgia
Dennis Allen Jewett, M.D.
Neurologist on Staff
Pamela E. Binkerd
Borgess Medical Center
Staff Research Associate I11
Kalamazoo, Michigan
California Primate Research Center
Associate Clinical Instructor
Davis , California
College of Human Medicine
Michigan State University
M. D. Daniel, D.V.M. Ph.D.
East Lansing, Michigan
Principal Associate in Microbiology
and Molecular Genetics
Member, Faculty of Medicine
Norval W. King, Jr., D.V.M.
New England Regional Primate
Associate Professor of Comparative
Research Center
Pathology
Harvard Medical School
Associate Director for Collaborative
Southborough, Massachusetts
Research
New England Regional Primate
W. Richard Dukelow, Ph.D.
Research Center
Professor and Director
Harvard Medical School
Endocrine Research Unit
Southborough, Massachusetts
Michigan State University
East Lansing, Michigan
H. K. Massel
Andrew G. Hendrickx, Ph.D. Department of Psychology
Research Physiologist and Associate Georgia State University
Director Atlanta, Georgia
California Primate Research Center
Davis , California
Duane M. Rumbaugh, Ph.D.
Charles F. Howard, Jr., Ph.D. Professor and Chairman
Scientist Department of Psychology
Department of Nutrition and Metabolic Georgia State University
Diseases Affiliated Scientist
Oregon Regional Primate Research Yerkes Regional Primate Research
Center Center of Emory University
Beaverton, Oregon Atlanta, Georgia
TABLE OF CONTENTS
Chapter 1
Diabetes and Carbohydrate Impairment in Nonhuman Primates .............. 1
Charles F. Howard, Jr.
Chapter 2
Movement Disorders ..................................................3 7
Dennis Allen Jewett
Chapter 3
Nonhuman Primates as Models for Human Viral Disease ....................4 5
M. D. Daniel, N. W. King, and R. D. Hunt
Chapter 4
The Nonhuman Primate as a Reproductive Model for Man .................. 79
W. Richard Dukelow
Chapter 5
Research in a Breeding Colony ......................................... l07
Irwin S. Bernstein
Chapter 6
Teratology and Birth Defects ...........................................l 31
Andrew G. Hendrickx and Pamela E. Binkerd
Chapter 7
Learning and Language Acquisition in Primates ........................... l59
Duane M. Rumbaugh and H. K. Massel
Index .............................................................1.9 1

Chapter 1
DIABETES AND CARBOHYDRATE IMPAIRMENT
IN NONHUMAN PRIMATES
. .
Charles F Howard. Jr
TABLE OF CONTENTS
I . Introduction ...................................................2. .
I1 . Defining Diabetes Mellitus in Human Beings and Primates ..............2
A . Metabolic and Hormonal Criteria in Nonhuman Primates ..........3
1. Glucose ............................................3.
2 . Lipids .............................................3.
3 . Ketones ............................................3.
4 . Hormones ..........................................6.
B . Secondary Manifestations ...................................7.
C . Secretory Cells and Morphology ..............................7.
I11 . Spontaneous Diabetes in Primates ..................................8.
A . Minimal Diagnoses ........................................8.
B . Documented Diagnoses .....................................8.
1. Papio hamudryas (Sacred Baboon) .......................9
2 . Macaca nemistrina (Pig-Tailed Macaque) .................9
3 . Macaca mulatta (Rhesus Macaque) .....................9.
4 . Macaca fascicularis (Cynomolgus or Crab-Eating Macaque) . 10
5 . Macaca nigra [Celebes Black Apes (Macaques)] ..........1 0
6 . Saimiri sciureus (Squirrel Monkeys) ..................... 11
7 . Prosimians .......................................... 12
8 . Pan troglodytes (Chimpanzee) ..........................1 2
IV . Induced Diabetes in Primates .....................................1.2
A . Pancreatectomy ...........................................1.2
B . Diabetes Induced with Alloxan ...............................1 4
C . Streptozotocin (STZ)-Induced Diabetes ........................1 5
D . Diabetes Induced by Hypothalamic Lesions .....................1 7
E . Miscellaneous ............................................1.7
V . Carbohydrate Impairment ........................................1.8
A . Hemorrhagic Shock .......................................1.8
B . Infection ................................................1.8
C . Stress ...................................................1.8
D . Pharmacological Agents ....................................1.9
E . Endocrine Effects ..........................................1 9
1. Pregnancy and Estrogenic Hormones ....................2 0
2 . Adrenal Hormones ..................................2.0
3 . Pituitary Hormones ...................................2 1
4 . Brain and Nervous System ............................2 1
5 . Hypothalamus ......................................2.1