Comparative and Laboratory Animal Medicine Commons^™

Mechanical Conflict System: A Novel Operant Method For The Assessment Of Nociceptive Behavior, Steven E. Harte, Jessica B. Meyers, Renee R. Donahue, Bradley K. Taylor, Thomas J. Morrow

Physiology Faculty Publications

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine …

The Pathology Of The Feline Model Of Mucopolysaccharidosis I, Mark E. Haskins, Gustavo D. Aguirre, Peter F. Jezyk, Robert J. Desnick, Donald F. Patterson

Gustavo D. Aguirre, VMD, PhD

Five cats with feline α-L-iduronidase-deficient mucopolysaccharidosis were studied. Membrane-bound cytoplasmic inclusions were present in central nervous system neurons, hepatocytes, chondrocytes, vascular and splenic smooth muscle cells, bone marrow leukocytes, and fibroblasts of the skin, eye, and cardiac valves. The lesions in these cats closely resemble those described in human patients with mucopolysaccharidosis I H (Hurler syndrome).

Comparative Genomic Mapping Of Uncharacterized Canine Retinal Ests To Identify Novel Candidate Genes For Hereditary Retinal Disorders, Barbara Zangerl, Jennifer L. Johnson, Jarek Pillardy, Qi Sun, Catherine André, Francis Galibert, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Purpose: To identify the genomic location of previously uncharacterized canine retina-expressed expressed sequence tags (ESTs), and thus identify potential candidate genes for heritable retinal disorders. Methods: A set of over 500 retinal canine ESTs were mapped onto the canine genome using the RHDF5000–2 radiation hybrid (RH) panel, and the resulting map positions were compared to their respective localization in the CanFam2 assembly of the canine genome sequence. Results: Unique map positions could be assigned for 99% of the mapped clones, of which only 29% showed significant homology to known RefSeq sequences. A comparison between RH map and sequence assembly indicated …

Cloning And Characterization Of The Canine Photoreceptor Specific Cone-Rod Homeobox (Crx) Gene And Evaluation As A Candidate For Early Onset Photoreceptor Diseases In The Dog, Novrouz B. Akhmedov, Victoria Baldwin, Barbara Zangerl, James K. Kijas, Linda S. Hunter, Katayoun D. Minoofar, Cathryn Mellersh, Elaine A. Ostrander, Gregory M. Acland, Debora B. Farber, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE: The cone-rod homeobox protein (CRX) is a member of the homeodomain-containing protein family expressed in the retinal photoreceptors and pinealocytes; it is involved in the regulation of the coordinate expression of multiple photoreceptor specific genes during retinal development. Mutations in the CRX gene are causally associated with retinal degeneration phenotypes in man. To clone the full length cDNA, characterize the genomic organization of canine CRX, map the gene in a radiation hybrid (RH) panel, and evaluate it as a candidate for canine inherited retinal degenerations. METHODS: cDNA representational difference analysis (RDA) was done using normal and cone degeneration (cd) …

Therapeutic Neonatal Hepatic Gene Therapy In Mucopolysaccharidosis Vii Dogs, Katherine Parker Ponder, John R. Melniczek, Lingfei Xu, Margaret A. Weil, Thomas M. O'Malley, Patricia A. O'Donnell, Van W. Knox, Gustavo D. Aguirre, Hamutal Mazrier, N Matthew Ellinwood, Margaret M. Sleeper, Albert M. Maguire, Susan W. Volk, Robert L. Mango, Jean Zweigle, John H. Wolfe, Mark E. Haskins

Gustavo D. Aguirre, VMD, PhD

Dogs with mucopolysaccharidosis VII (MPS VII) were injected intravenously at 2–3 days of age with a retroviral vector (RV) expressing canine β-glucuronidase (cGUSB). Five animals received RV alone, and two dogs received hepatocyte growth factor (HGF) before RV in an attempt to increase transduction efficiency. Transduced hepatocytes expanded clonally during normal liver growth and secreted enzyme with mannose 6-phosphate. Serum GUSB activity was stable for up to 14 months at normal levels for the RV-treated dogs, and for 17 months at 67-fold normal for the HGF/RV-treated dog. GUSB activity in other organs was 1.5–60% of normal at 6 months for …

Radiation Hybrid Mapping Of Cataract Genes In The Dog, Linda S. Hunter, Duska J. Sidjanin, Jennifer L. Johnson, Barbara Zangerl, Francis Galibert, Catherine Andre, Ewen Kirkness, Elijah Talamas, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Purpose: To facilitate the molecular characterization of naturally occurring cataracts in dogs by providing the radiation hybrid location of 21 cataract-associated genes along with their closely associated polymorphic markers. These can be used for segregation testing of the candidate genes in canine cataract pedigrees. Methods: Twenty-one genes with known mutations causing hereditary cataracts in man and/or mouse were selected and mapped to canine chromosomes using a canine:hamster radiation hybrid RH5000 panel. Each cataract gene ortholog was mapped in relation to over 3,000 markers including microsatellites, ESTs, genes, and BAC clones. The resulting independently determined RH-map locations were compared with the …

Immunolocalization Of Ciliary Neurotrophic Factor Receptor Α (Cntfrα) In Mammalian Photoreceptor Cells, William Beltran, Hermann Rohrer, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE: To characterize the site of expression of the α subunit of the receptor for ciliary neurotrophic factor (CNTFRα) in the retina of a variety of mammalian species, and determine whether CNTFRα is localized to photoreceptor cells. METHODS: The cellular distribution of CNTFRα (protein) was examined by immunocytochemistry in the adult retinas of several mammalian species that included mouse, rat, dog, cat, sheep, pig, horse, monkey, and human. Developing retinas from 3-day-old and 6-day-old rats were also included in this study. The molecular weight of CNTFRα in rat, dog, cat, pig, and human retinas was determined by immunoblotting. RESULTS: CNTFRα …

Congenital Stationary Night Blindness In The Dog: Common Mutation In The Rpe65 Gene Indicates Founder Effect, Gustavo D. Aguirre, Victoria Baldwin, Sue Pearce-Kelling, Kristina Narfström, Kunal Ray, Gregory M. Acland

Gustavo D. Aguirre, VMD, PhD

Purpose: To clone and characterize the canine RPE65 cDNA from normal dog, examine for mutations, and establish if the mutation identified in Swedish briard dogs with retinal dystrophy is present in dogs of the same breed that originated from the United States and other countries, and are affected with congenital stationary night blindness. Methods: Fifteen briard dogs were studied, of which 10 were affected with csnb, and five were clinically normal. In addition, we tested samples from four Swedish dogs, and samples from a briard affected with progressive retinal atrophy. RPE65 cDNA was cloned a from retinal cDNA library by …

Canine And Human Visual Cortex Intact And Responsive Despite Early Retinal Blindness From Rpe65 Mutation, Geoffrey K. Aguirre, András M. Komáromy, Artur V. Cideciyan, David H. Brainard, Tomas S. Aleman, Alejandro J. Roman, Brian B. Avants, James C. Gee, Marc Korczykowski, William W. Hauswirth, Gregory M. Acland, Gustavo D. Aguirre, Samuel G. Jacobson

Gustavo D. Aguirre, VMD, PhD

Background RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA). Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans …

Cloning Of The Canine Abca4 Gene And Evaluation In Canine Cone-Rod Dystrophies And Progressive Retinal Atrophies, James K. Kijas, Barbara Zangerl, Brian Miller, Jacque Nelson, Ewen F. Kirkness, Gustavo D. Aguirre, Gregory M. Acland

Gustavo D. Aguirre, VMD, PhD

PURPOSE: To characterize a novel early onset canine retinal disease, and evaluate the ATP-binding cassette transporter gene ABCA4 as a potential candidate gene in this and other canine retinal degenerations. METHODS: Retinal disease was characterized ophthalmoscopically and electroretinographically in two pit bull terrier dogs and their purpose-bred descendants. All 50 exons of the canine ABCA4 gene were amplified, cloned and sequenced from retinal mRNA of a normal, a carrier and an affected animal, and polymorphisms identified. The latter were used to search for association between ABCA4 and retinal disease both within the study pedigrees and in additional canine breeds segregating …

Cloning And Characterization Of Canine Pax6 And Evaluation As A Candidate Gene In A Canine Model Of Aniridia, Linda S. Hunter, Duska J. Sidjanin, Manuel Villagrasa Hijar, Jennifer L. Johnson, Ewen Kirkness, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Purpose: Mutations in PAX6 cause human aniridia. The small eye (sey) mouse represents an animal model for aniridia. However, no large animal model currently exists. We cloned and characterized canine PAX6, and evaluated PAX6 for causal associations with inherited aniridia in dogs. Methods: Canine PAX6 was cloned from a canine retinal cDNA library using primers designed from human and mouse PAX6 consensus sequences. An RH3000 radiation hybrid panel was used to localize PAX6 within the canine genome. Genomic DNA was extracted from whole blood of dogs with inherited aniridia, and association testing was performed using markers on CFA18. Fourteen PAX6 …

Calcium Channel Blocker D-Cis-Diltiazem Does Not Slow Retinal Degeneration In The Pde6b Mutant Rcd1 Canine Model Of Retinitis Pigmentosa, Susan E. Pearce-Kelling, Tomas S. Aleman, Amanda Nickle, Alan M. Laties, Gustavo D. Aguirre, Samuel G. Jacobson, Gregory M. Acland

Gustavo D. Aguirre, VMD, PhD

Purpose: D-cis-diltiazem, a calcium channel blocker, has been reported to enhance photoreceptor survival in the rd mouse, a model of retinitis pigmentosa (RP) resulting from mutation of the PDE6B gene. We tested the hypothesis that diltiazem treatment would similarly rescue the canine rcd1 model of RP, which is also caused by a null mutation in the PDE6B gene. Methods: D-cis-diltiazem was delivered orally twice daily to rcd1 affected dogs beginning at 4 weeks of age; untreated age-matched rcd1 dogs served as controls. At 14 weeks, electroretinograms (ERG) were performed on all animals; 14 dogs were euthanized at this age, and …

Animal Model Of Human Disease: Mucopolysaccharidosis Type Vii (Sly Syndrome). Beta-Glucuronidase-Deficient Mucopolysaccharidosis In The Dog, Mark E. Haskins, Gustavo D. Aguirre, Peter F. Jezyk, Edward H. Schuchman, Robert J. Desnick, Donald F. Patterson

Gustavo D. Aguirre, VMD, PhD

No abstract provided.

Analysis Of Six Candidate Genes As Potential Modifiers Of Disease Expression In Canine Xlpra1, A Model For Human X-Linked Retinitis Pigmentosa 3, Richard Guyon, Susan E. Pearce-Kelling, Caroline J. Zeiss, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Purpose: Canine X-linked progressive retinal atrophy (XLPRA) is caused by mutations in RPGR exon ORF15, which is also a mutation hotspot in human X-linked retinitis pigmentosa 3 (RP3). The XLPRA1 form of disease has shown extensive phenotypic variability in a colony of dogs that all inherited the same mutant X-chromosome. This variability in onset and severity makes XLPRA1 a valuable model to use to identify genes influencing photoreceptors degeneration in dog and to elucidate molecular mechanisms underlying RP in its human homolog. In this study, RPGRIP1, RANBP2, NPM1, PDE6D, NPHP5, and ABCA4 genes were selected on the basis of interaction …

Animal Mourning: Précis Of How Animals Grieve (King 2013), Barbara J. King

Animal Sentience

Abstract: When an animal dies, that individual’s mate, relatives, or friends may express grief. Changes in the survivor’s patterns of social behavior, eating, sleeping, and/or of expression of affect are the key criteria for defining grief. Based on this understanding of grief, it is not only big-brained mammals like elephants, apes, and cetaceans who can be said to mourn, but also a wide variety of other animals, including domestic companions like cats, dogs, and rabbits; horses and farm animals; and some birds. With keen attention placed on seeking where grief is found to occur and where it is absent …

The Human Intruder Test: An Anxiety Assessment In Rhesus Macaques (Macaca Mulatta), Emily J. Peterson

Masters Theses

The human intruder test (HIT) is a noninvasive tool widely used for assessing anxiety in rhesus macaques (Macaca mulatta). This thesis explores the HIT procedure and applies it to a population of monkeys with a self-injurious behavioral pathology. Individual variation on this test can be used to assess anxiety and temperament. The first experiment of this thesis applied two different procedures of the HIT to 17 monkeys at UMass. Monkeys displayed little response to the intruder, and no significant differences were detected for the two procedures. To determine whether these responses were unique to the UMass monkeys, their …

Psychology And Its Animal Subjects, Kenneth J. Shapiro

Kenneth J. Shapiro, PhD

By way of introducing Psychologists for the Ethical Treatment of Animals (PsyETA) to readers of the journal, I have been asked to make some comments about the organization and, from a personal point of view, to suggest some of my own positions and views.

The Harmful, Nontherapeutic Use Of Animals In Research Is Morally Wrong, Nathan Nobis

Nathan M. Nobis, PhD

It is argued that using animals in research is morally wrong when the research is nontherapeutic and harmful to the animals. This article discusses methods of moral reasoning and discusses how arguments on this and other bioethical issues might be defended and critiqued. A basic method of moral argument analysis is presented and used to show that common objections to the view that “animal research is morally wrong” fail: ie, common arguments for the view that “animal research is morally permissible” are demonstrably unsound or in need of defense. It is argued that the best explanations why harmful, nontherapeutic research …

Interests And Harms In Primate Research, Nathan Nobis

Nathan M. Nobis, PhD

The article discusses the moral issues on primate research in reference to the moral defenses by Sughrue and colleagues. It states that Sughrue and colleagues have claimed to provide equal examination of the primate stroke research's ethics. It mentions that the promise to straighten out a number of ethical arguments in favor and against primate research was not fulfilled. Several moral arguments are presented in response to Sughrue and colleagues' moral defense for animal experimentation.

Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens

Andrew N. Rowan, DPhil

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation.

This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress …