Publications by authors named "Jason S Villano"

13 Publications

  • Page 1 of 1

Acepromazine and Chlorpromazine as Pharmaceutical-grade Alternatives to Chlorprothixene for Pupillary Light Reflex Imaging in Mice.

J Am Assoc Lab Anim Sci 2020 03 8;59(2):197-203. Epub 2020 Jan 8.

Department of Ophthalmology and Visual Sciences, and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan;, Email:

Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm s; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.
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http://dx.doi.org/10.30802/AALAS-JAALAS-19-000094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073400PMC
March 2020

Assessment of Mouse Handling Techniques During Cage Changing.

J Am Assoc Lab Anim Sci 2019 11 23;58(6):767-773. Epub 2019 Oct 23.

Refinement Enrichment Advancements Laboratory, Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan.

Mouse handling during cage changing and health evaluation has traditionally been performed by using forceps. This method was adopted as a biosecurity measure but can adversely affect employee ergonomics and rodent behavior. In this study, we evaluated alternative methods of rodent handling and their potential implications for efficiency, biosecurity, and animal welfare. Study groups included plastic cups, gloved hands, 2 methods of tunnel handling, and forceps. Evaluations included speed of cage change, ATP-based assessment of sanitization, and retrospective analysis of colony health and breeding data. The time to change 14 cages was significantly faster at each time point for the gloved hands and forceps groups as compared with the other methods. Overall speed did not increase significantly with each subsequent study week for any group. ATP levels after sanitization with hydrogen peroxide-peracetic acid mixture differed significantly between gloves and forceps. When ATP level was evaluated on a per-cm² basis, no significant difference between gloves and forceps was detected. Although tunnel and cup handling both increased the time for cage-changing, the tunnel served as both an indirect handling method and a shelter when left within the cage. Retrospective analysis revealed that breeding performance and colony health were similar among groups. Although efficiency is a concern for large-scale implementation of novel handling methods, the tunnel method may prove beneficial for sensitive strains or studies requiring indirect handling. In addition, using gloved hands to directly handle mice during cage changing is efficient and avoids the ergonomic strain associated with forceps. Precautions should be taken when handling mice with gloves, given that the increased contact area carries an increased load of organic debris. Changing gloves between rack sides or before proceeding to the animals belonging to a different investigator minimizes the potential for cross-contamination.
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http://dx.doi.org/10.30802/AALAS-JAALAS-19-000015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926398PMC
November 2019

Variation in Bacterial Contamination of Microisolation Cage Tops According to Rodent Species and Housing System.

J Am Assoc Lab Anim Sci 2019 07 7;58(4):450-455. Epub 2019 May 7.

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan;, Email:

The recommends sanitizing cage components, including microisolation cage tops (MCT), at a minimum of every 2 wk. Previously published data demonstrated that mouse MCT microbial loads do not increase until at least 2 wk and that sanitation can be delayed past 2 wk. How microbial loads differ on mouse compared with rat MCT, as well as across different ventilation systems, remains unclear. We hypothesized that MCT microbial loads would be higher in tops from rats compared with mice and would differ according to IVC ventilation system. We evaluated bacterial loads on MCT at serial time points to 90 d from static cages housing mice or rats and from rat and mouse cages on several ventilation systems (mice, 6; rats, 4). MCT were determined to have sufficiently elevated bacterial loads to necessitate changing based on either statistically significant changes in bacterial loads or values greater than 50 cfu. Across all ventilation systems, bacterial counts at 14 d were significantly higher on rat MCT compared with mouse MCT. Across the ventilation systems examined, rat MCT cfu remained similarly elevated from 14 d through 90 d. Mouse MCT total cfu were also stable across multiple ventilation systems yet remained lower than 50 cfu until at least 90 d. Patterns of bacterial species isolated from rat MCT were relatively consistent over time and ventilation system, whereas mice showed greater variability in both contexts. We found that 14 d is an appropriate sanitization time point for rat MCT, whereas the interval at which mouse MCT are cleaned can be extended to 90 d at least. Our data highlight interspecies differences in the accumulation of bacteria on MCT and that mouse MCT sanitation intervals for several housing systems can be extended beyond 14 d.
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http://dx.doi.org/10.30802/AALAS-JAALAS-18-000126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643085PMC
July 2019

Outbreak of Murine Infection with Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet.

mSphere 2019 03 20;4(2). Epub 2019 Mar 20.

Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a strain of ribotype 027 that we term 16N203. infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, the presence of bacteria in fecal/colonic culture, and detection of toxins. F1 mice from parents fed the methyl supplementation diet also had significantly reduced survival ( < 0.0001) compared with F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of in association with a pre- and perinatal methyl donor diet suggest the important role that diet may play in host defense and CDI risk factors. infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of animals with antibiotics to establish disease. The outbreak that we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated with a pre- and perinatal methyl supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain that we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.
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http://dx.doi.org/10.1128/mSphereDirect.00138-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429045PMC
March 2019

Safety Considerations When Working with Humanized Animals.

ILAR J 2018 12;59(2):150-160

Unit for Laboratory Animal Medicine, University of Michigan Medical School in Ann Arbor, Michigan.

Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. With this technology comes the need for the animal research enterprise to understand the inherent and potential risks, such as exposure to bloodborne pathogens, associated with the model development and research applications. Here, we review existing humanized animal models and provide recommendations for their safe use based on regulatory framework and literature. A risk assessment program-from handling the human material to its administration to animals and animal housing-is a necessary initial step in mitigating risks associated with the use of humanized animals in research. Ultimately, establishing institutional policies and guidelines to ensure personnel safety is a legal and ethical responsibility of the research institution as part of the occupational health and safety program and overall animal care and use program.
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http://dx.doi.org/10.1093/ilar/ily012DOI Listing
December 2018

Viral Vector Biosafety in Laboratory Animal Research.

Comp Med 2017 Jun;67(3):215-221

University of Michigan, Ann Arbor, Michigan;, Email:

Viral vector research presents unique occupational health and safety challenges to institutions due to the rapid development of both in vivo and in vitro gene-editing technologies. Risks to human and animal health make it incumbent on institutions to appropriately evaluate viral vector usage in research on the basis of available information and governmental regulations and guidelines. Here we review the factors related to risk assessment regarding viral vector usage in animals and the relevant regulatory documents associated with this research, and we highlight the most commonly used viral vectors in research today. This review is particularly focused on the background, use in research and associated health and environmental risks related to adenoviral, adeno-associated viral, lentiviral, and herpesviral vectors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482513PMC
June 2017

Personal Protective Equipment in Animal Research.

Comp Med 2017 Jun;67(3):203-214

INDA - The Association of the Nonwoven and Engineered Fabrics Industry, Cary, North Carolina.

The occupational health and safety program is an integral component of a comprehensive animal care and use program. It is important to mitigate the risk of exposures of animal care and research personnel to allergens and physical, chemical, radiologic, and biologic hazards during the conduct of various tasks. This need is especially true in infectious disease and biocontainment research. One aspect of the program is the provision of personal protective equipment (PPE). Commercially available PPE should be carefully evaluated based on their material composition and performance according to manufacturer data. To help institutions and end users by providing them guidance on choosing appropriate PPE, we here discuss the regulatory framework, device standards, and materials engineering for various PPE, including gloves, shoe covers, head caps, gowns, aprons, masks, hearing and eye protection devices, and respirators. Ultimately, the choice of appropriate PPE is based on the risk assessment, which should include consideration for personnel comfort, correct device fitting, and the containment level for the hazard used.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482512PMC
June 2017

Special Issue: Infectious Disease Research: Animal Models and Risk Management.

Comp Med 2017 06;67(3):189-191

SingHealth Experimental Medicine Centre, Singapore Health Services Pte Ltd, Singapore.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482510PMC
June 2017

Clinical Assessment of Urinary Tract Damage during Sustained-Release Estrogen Supplementation in Mice.

Comp Med 2017 02;67(1):11-21

Unit for Laboratory Animal Medicine (ULAM), University of Michigan, Ann Arbor, Michigan;, Email:

Estrogen supplementation is a key component of numerous mouse research models but can adversely affect the urinary system. The goal of this study was to develop a clinical scoring system and identify biomarkers of occult urinary tract lesions prior to the development of systemic illness in mice. Ovariectomized or sham-surgery SCID mice were implanted subcutaneously with a placebo pellet or one containing sustained-release estradiol (0.18 mg 60-d release 17β-estradiol). Mice were assessed twice weekly for 4 to 6 wk by using a clinical scoring system that included body condition, general activity, posture, hair coat, hydration, abdominal distension, urine staining of coat and skin, and ability to urinate. Samples were collected weekly for urinalysis, BUN, creatinine, and serum estradiol levels. Terminal samples were analyzed for histopathologic lesions. Compared with placebo controls, estradiolsupplemented mice had higher serum estradiol levels at weeks 2 and 3; significant differences in total clinical scores by the 3-wk time point; and in body condition, general activity, posture, hair coat, and urine staining scores by the 6-wk terminal time point. Urinary tract lesions included hydronephrosis, pyelonephritis, cystitis, and urolithiasis. All mice with urolithiasis had crystalluria, and 5 of the 6 mice with pyelonephritis or hydroureter had dilute urine (that is, specific gravity less than 1.030). However, these findings were not specific to mice with lesions. A total clinical score of 3.5 (maximum, 24) identified estradiol-supplemented mice with 83% specificity and 50% sensitivity, but no single clinical parameter, biomarker, or the total clinical score accurately predicted occult urinary tract lesions. Considering the lesions we observed, prudence is warranted when using pelleted sustained-release estradiol in mice, and important parameters to monitor for animal health include urine staining, body condition score, urine sediment, and urine specific gravity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310620PMC
February 2017

Bacterial infections in Myd88-deficient mice.

Comp Med 2014 Apr;64(2):110-4

Department of Comparative Medicine, Penn State Hershey Medical Center, College of Medicine, Hershey, Pennsylvania.

Three breeding colonies of Myd88(-/-) mice had a history of significant morbidity and mortality. Although strain-specific poor reproductive performance might explain neonatal death and dystocia, mice were found dead or required euthanasia because of moribundity, distended abdomen, head tilt, and seizures. Histopathology results included bacteremia, placentitis, metritis, peritonitis with abscess formation, and suppurative meningoencephalitis. Intralesional gram-negative coccobacilli were present, often in extremely high number. Cultures of samples of the cardiac blood of a mouse and from water-bottle sipper tubes provided to some affected mice grew Pseudomonas aeruginosa. In addition, affected tissues from 2 mice and feces from a third tested PCR-positive for P. aeruginosa. Although the mice had received autoclaved reverse-osmosis-purified drinking water, we suspect that the mice were inoculated with P. aeruginosa through contaminated sipper tubes. Because of the deficiency in most of the Toll-like receptor signaling pathways, these Myd88(-/-) mice were unlikely to have developed competitive innate and adaptive immune responses, resulting in bacterial infections. These clinical cases underscore the importance of understanding how genotype, phenotype and environment affect animal health. Sound husbandry and experimental practices are needed to prevent the exposure of immuno-deficient mice to pathogens.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997288PMC
April 2014

Mandibular fracture and necrotizing sialometaplasia in a rabbit.

Comp Med 2013 Feb;63(1):67-70

Department of Comparative Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA.

A 7-mo-old female New Zealand white rabbit presented with hemorrhage of the gingiva surrounding a loose lower right incisor. Antemortem conventional radiographs revealed only a small bone fragment adjacent to the left mandible's body. In light of a provisional diagnosis of mandibular fracture, the rabbit was euthanized. Postmortem radiographs of the disarticulated mandible demonstrated mandibular symphyseal fracture and comminuted fracture of the ramus and body of the left mandible. According to histopathology, the left submandibular salivary gland had necrotizing sialometaplasia, a nonneoplastic condition of the salivary glands that is caused by ischemic infarction. Although rabbits have been used as animal models of mandibular fracture and necrotizing sialometaplasia, no nonexperimental case of such conditions had been reported previously.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567379PMC
February 2013

Complications of elastase-induced arterial saccular aneurysm in rabbits: case reports and literature review.

Comp Med 2012 Dec;62(6):480-6

Department of Comparative Medicine, Penn State Hershey Medical Center, Hershey, PA, USA.

Endoluminal infusion and incubation of elastase with or without collagenase into the rabbit common carotid artery is an established model of arterial saccular aneurysm. The model mimics naturally occurring human cerebral aneurysms in many ways, including histologic and morphologic characteristics, hemodynamic pressures, and shear stresses. However, complications have been associated with the model. Here, we report 2 complications: 1) the first known case of iatrogenic laryngeal hemiplegia in a rabbit; and 2) histopathologically confirmed iatrogenic hippocampal and cerebellar infarcts (stroke). Finally, we present and review data from current literature on the morbidity and mortality associated with this model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527752PMC
December 2012

Morphometrics and pelage characterization of longtailed macaques (Macaca fascicularis) from Pulau Bintan, Indonesia; Singapore; and Southern Vietnam.

J Am Assoc Lab Anim Sci 2009 Nov;48(6):727-33

SingHealth Experimental Medicine Centre, National University of Singapore, Singapore.

Cynomolgus (or longtailed) macaques (Macaca fascicularis) are used extensively as laboratory animals in biomedical research. Their use in Singapore, an emerging biomedical hub in Southeast Asia, is now increasing widely, with research subjects currently originating from Singapore, Vietnam, and Pulau Bintan, Indonesia. Limited data exist on the genetic and phenotypic polymorphisms and phylogenetic relationships of these groups, and the animals are used as research subjects without regard to potential differences or homogeneity. Here we characterize their phenotypes by using established primatology tools to detail morphometrics and pelage erythrism and saturation. Pelage analyses supported the Gloger rule, in which heavily pigmented forms predominate near the equator, with Singaporean and Bintan macaques having darker pelage than Vietnamese macaques. Morphometric variation patterns suggest a tendency toward insular dwarfism and correlate generally with the Bergmann rule, in which body mass increases with latitude and colder climate. Although the 3 populations all belong to the nominotypical subspecies M. f. fascicularis, phenotypic differences are evident and are valuable tools to analyze their phylogeographic history and phylogenetic relationships.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786926PMC
November 2009