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Veterinary Sciences
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Animal and Disease Models in Biomedical Research
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Animal and Disease Models in Biomedical Research

A special issue of Veterinary Sciences (ISSN 2306-7381). This special issue belongs to the section "Veterinary Biomedical Sciences".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 22845

Special Issue Editor

Dr. Emrah Yatkin

E-Mail Website
Guest Editor
Central Animal Laboratory, Faculty of Medicine, University of Turku, FI-20014 Turku, Finland
Interests: Laboratory animal science; experimental disease models; prostate inflammation and cancer; GLP; toxicology; animal welfare
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Spontaneous and induced animal models have significantly contributed to scientific developments and improvement of human and animal health.

Scientists usually utilize one or more of the scientific methods including in vitro, in silico, vertebrate and non-vertebrate in vivo models. Veterinary clinical patients have increasingly been used as models of disease treatments.

However, the concern about the reproducibility and translatability of animal models has been increasingly addressed both in the scientific community and society. Reproducibility and bench-to-bedside translatability of preclinical research relies on understanding the relevance and limitations and continuous efforts to improve animal models.

This Special Issue welcomes original research articles and review articles dealing with emerging factors affecting the reproducibility and translatability of animal models such as standardization and design of animal experiments, interpretation of experimental data, genetic drift, environmental factors, gut microbiota, animal handling techniques, and hygienic conditions of animal facilities. Topics can also include the development and validation of alternative models for animals and the use of animals as disease models and animal welfare.

Dr. Emrah Yatkin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Veterinary Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal models
  • animal welfare and the 3Rs
  • alternative models
  • animal disease models
  • laboratory animals
  • model validation
  • reproducibility

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Published Papers (7 papers)

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Research

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15 pages, 3949 KiB  
Article
Effect and Mechanism of siRNAs Targeting IL-1β/TNF-α Combined with BMSCs Transplantation in Ameliorating Rheumatoid Arthritis in Rats
by Shifeng Pan, Lijun Wang, Bingxing Wu and Hua Xing
Vet. Sci. 2022, 9(10), 531; https://doi.org/10.3390/vetsci9100531 - 28 Sep 2022
Cited by 2 | Viewed by 2755
Abstract
Background: Rheumatoid arthritis (RA) is an autoimmune disease. Bone marrow mesenchymal stem cells (BMSCs) have multilineage differentiation and anti-inflammatory potential, and small interfering RNAs (siRNAs) can inhibit the target gene expression, which make them suitable for ameliorating RA. The current study was aimed [...] Read more.
Background: Rheumatoid arthritis (RA) is an autoimmune disease. Bone marrow mesenchymal stem cells (BMSCs) have multilineage differentiation and anti-inflammatory potential, and small interfering RNAs (siRNAs) can inhibit the target gene expression, which make them suitable for ameliorating RA. The current study was aimed to explore the effect and potential mechanisms of siRNAs targeting IL-1β/TNF-α combined with BMSCs transplantation in ameliorating RA in rats. Methods: Collagen-induced arthritis (CIA) model rats were randomly divided into five groups: PBS (Model control group), methotrexate (Positive drug treatment group), BMSCs (BMSCs transplantation group), siRNA (IL-1β/TNF-α siRNAs injection group), siRNA + BMSCs (Both IL-1β/TNF-α siRNAs injection and BMSCs transplantation group). After treatment for 0, 7, 14, 21, 28 days, the ameliorating effect was comprehensively assessed through results of the body weight, toe swelling value, the immobility time of forced swimming, the serum concentrations of IL-1β and TNF-α, knee joint DR-X imaging and pathological analysis as well as of IL-1β, TNF-α and NF-κB mRNA expression in spleen tissue. Furthermore, the potential underlying mechanism involving the NF-κB signaling pathways was also explored. Results: Compared with the PBS group, BMSCs, siRNA, siRNA + BMSCs treatment groups showed significant lower toe swelling value, immobility time, spleen index, serum contents of IL-1β and TNF-α. In addition, the DR-X results showed that the knee carton surface tended to smoothing without bone hyperplasia, suggesting that these three treatments were all able to successfully ameliorate RA symptoms. In addition, compared with the PBS group, the protein expression of p-NF-κB-p65 was significantly reduced in the knees of siRNA + BMSCs rats. BMSCs labeled with BrdU were also found in the knees of rats. Moreover, the mRNA expression of IL-1β, TNF-α and NF-κB-P65 in spleen tissue of siRNA + BMSCs rats were all significantly inhibited. Conclusions: Our results demonstrated for the first time that siRNA + BMSCs was able to ameliorate RA inflammation by inhibiting the activation of NF-κB signaling pathways and reducing the erosion of articular cartilage, and siRNA + BMSCs treatment showed synergism effects in helping ameliorating the inflammation and cartilage repair of RA rats. Therefore, the results of our present study provide a new idea for gene and stem cell therapy for RA. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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23 pages, 6231 KiB  
Article
Dextran Sulphate Sodium Acute Colitis Rat Model: A Suitable Tool for Advancing Our Understanding of Immune and Microbial Mechanisms in the Pathogenesis of Inflammatory Bowel Disease
by Petra Adamkova, Petra Hradicka, Helena Kupcova Skalnikova, Veronika Cizkova, Petr Vodicka, Silvia Farkasova Iannaccone, Monika Kassayova, Sona Gancarcikova and Vlasta Demeckova
Vet. Sci. 2022, 9(5), 238; https://doi.org/10.3390/vetsci9050238 - 16 May 2022
Cited by 8 | Viewed by 4624
Abstract
Inflammatory bowel disease (IBD) is a group of disorders causing inflammation in the digestive tract. Recent data suggest that dysbiosis may play a pivotal role in the IBD pathogenesis. As microbiome-based therapeutics that modulate the gut ecology have been proposed as a novel [...] Read more.
Inflammatory bowel disease (IBD) is a group of disorders causing inflammation in the digestive tract. Recent data suggest that dysbiosis may play a pivotal role in the IBD pathogenesis. As microbiome-based therapeutics that modulate the gut ecology have been proposed as a novel strategy for preventing IBD, the aim of presenting study was to evaluate the dextran sulphate sodium (DSS) rat model mainly in terms of microbial shifts to confirm its suitability for dysbiosis study in IBD. Acute colitis was induced using 5% DSS solution for seven days and rats were euthanized five days after DSS removal. The faecal/caecal microbiota was analyzed by next generation sequencing. Disease activity index (DAI) score was evaluated daily. Blood and colon tissue immunophenotyping was assessed by flow cytometry and histological, haematological, and biochemical parameters were also evaluated. The colitis induction was reflected in a significantly higher DAI score and changes in all parameters measured. This study demonstrated significant shifts in the colitis-related microbial species after colitis induction. The characteristic inflammation-associated microbiota could be detected even after a five day-recovery period. Moreover, the DSS-model might contribute to an understanding of the effect of different treatments on extraintestinal organ impairments. The observation that certain bacterial species in the gut microbiota are associated with colitis raises the question of whether these organisms are contributors to, or a consequence of the disease. Despite some limitations, we confirmed the suitability of DSS-induced colitis model to monitor microbial changes during acute colitis, in order to test attractive new microbiome-based therapies. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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10 pages, 1984 KiB  
Article
Crocodylus porosus Sera a Potential Source to Identify Novel Epigenetic Targets: In Silico Analysis
by Ruqaiyyah Siddiqui, Jibran Sualeh Muhammad, Sutherland K. Maciver and Naveed Ahmed Khan
Vet. Sci. 2022, 9(5), 210; https://doi.org/10.3390/vetsci9050210 - 25 Apr 2022
Viewed by 2812
Abstract
We have previously found that sera from Crocodylus porosus contain anticancer agents and the treatment of MCF7 cells with this serum resulted in the differential expression of 51 genes. The purpose of this study was to use in silico analysis to identify genes [...] Read more.
We have previously found that sera from Crocodylus porosus contain anticancer agents and the treatment of MCF7 cells with this serum resulted in the differential expression of 51 genes. The purpose of this study was to use in silico analysis to identify genes that might be epigenetically modulated in cells treated with crocodile serum and to understand the role of potential genes as novel candidates with epigenetic therapeutic potential. The findings report five proto-oncogenes (TUBA1B, SLC2A1, PGK1, CCND1, and NCAPD2) and two tumor suppressor genes (RPLP2, RPL37) as novel therapeutic targets. Furthermore, we present a comprehensive overview of relevant studies on epigenetic regulation of these genes along with an insight into their clinical implications. Therefore, elucidating the molecules present in the serum and gut bacteria of reptiles such as crocodiles may offer insights into the role of these genes on longevity, health, disease, and life expectancy. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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12 pages, 3157 KiB  
Article
Atherosclerotic Lesion of the Carotid Artery in Indonesian Cynomolgus Monkeys Receiving a Locally Sourced Atherogenic Diet
by Sri Rahmatul Laila, Dewi Apri Astuti, Irma Herawati Suparto, Ekowati Handharyani, Thomas C. Register and Dondin Sajuthi
Vet. Sci. 2022, 9(3), 105; https://doi.org/10.3390/vetsci9030105 - 26 Feb 2022
Cited by 1 | Viewed by 2784
Abstract
The atherosclerotic lesion is a principal hallmark of atherosclerotic animal models. This study aimed to assess lesions of the carotid artery in Indonesian cynomolgus monkeys exposed to an IPB-1 atherogenic diet. A total of 20 adult male cynomolgus monkeys received the local IPB-1 [...] Read more.
The atherosclerotic lesion is a principal hallmark of atherosclerotic animal models. This study aimed to assess lesions of the carotid artery in Indonesian cynomolgus monkeys exposed to an IPB-1 atherogenic diet. A total of 20 adult male cynomolgus monkeys received the local IPB-1 diet for two years. Blood lipid profiles, morphology, and carotid ultrasound of monkeys were measured. Nine of them were euthanized to confirm atherosclerotic lesions. Common carotid arteries (CCA) and carotid bifurcation (BIF) samples were collected and stained using Verhoef-van Giessen and CD68 immunohistochemistry. The results reveal the presence of severe atherosclerosis plaques in six out of nine animals (66.7%) corresponding to intermediately and hyper-responsive groups. The hyper-responsive group displayed the highest response in the developing intimal area (IA) at the CCA (0.821 mm2), whereas the hyporesponsive group had the smallest IA (0.045 mm2) (p = 0.0001). At the BIF, the hyporesponsive group showed the smallest IA (p = 0.001), but there was no difference between the intermediately and hyper-responsive groups (p = 0.312). The macrophage marker CD68 was also expressed on the cartotid of the intermediately and hyper-responsive groups. These results indicate that severe atherosclerotic lesions with high infiltration of macrophages were formed in the carotid arteries of intermediately and hyper-responsive Indonesian cynomolgus monkeys fed with the local atherogenic diet IPB-1 over two years, thus confirming atherosclerosis in a nonhuman primate model. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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12 pages, 1771 KiB  
Article
Multiplexed Genome Editing for Efficient Phenotypic Screening in Zebrafish
by Shuyu Guo, Ge Gao, Cuizhen Zhang and Gang Peng
Vet. Sci. 2022, 9(2), 92; https://doi.org/10.3390/vetsci9020092 - 19 Feb 2022
Cited by 4 | Viewed by 2952
Abstract
Zebrafish are widely used to investigate candidate genes for human diseases. While the emergence of CRISPR-Cas9 technology has revolutionized gene editing, the use of individual guide RNAs limits the efficiency and application of this technology in functional genetics research. Multiplexed genome editing significantly [...] Read more.
Zebrafish are widely used to investigate candidate genes for human diseases. While the emergence of CRISPR-Cas9 technology has revolutionized gene editing, the use of individual guide RNAs limits the efficiency and application of this technology in functional genetics research. Multiplexed genome editing significantly enhances the efficiency and scope of gene editing. Herein, we describe an efficient multiplexed genome editing strategy to generate zebrafish mutants. Following behavioural tests and histological examination, we identified one new candidate gene (tmem183a) for hearing loss. This study provides a robust genetic platform to quickly obtain zebrafish mutants and to identify candidate genes by phenotypic readouts. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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Review

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12 pages, 1728 KiB  
Review
The Translational Role of Animal Models for Estrogen-Related Functional Bladder Outlet Obstruction and Prostatic Inflammation
by Risto Santti, Emrah Yatkin, Jenni Bernoulli and Tomi Streng
Vet. Sci. 2022, 9(2), 60; https://doi.org/10.3390/vetsci9020060 - 31 Jan 2022
Cited by 2 | Viewed by 2670
Abstract
The prevalence of LUTS and prostatic diseases increases with age both in humans and companion animals, suggesting that a common underlying cause of these conditions may be age-associated alterations in the balance of sex hormones. The symptoms are present with different and variable [...] Read more.
The prevalence of LUTS and prostatic diseases increases with age both in humans and companion animals, suggesting that a common underlying cause of these conditions may be age-associated alterations in the balance of sex hormones. The symptoms are present with different and variable micturition dysfunctions and can be assigned to different clinical conditions including bladder outlet obstruction (BOO). LUTS may also be linked to chronic non-bacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS), but the relationship between these conditions is unknown. This review summarizes the preclinical data that supports a role for excessive estrogen action in the development of obstructive voiding and nonbacterial prostatic inflammation. Preclinical studies that are emphasized in this review have unequivocally indicated that estrogens can induce functional and structural changes resembling those seen in human diseases. Recognizing excessive estrogen action as a possible hormonal basis for the effects observed at multiple sites in the LUT may inspire the development of innovative treatment options for human and animal patients with LUTS associated with functional BOO and CP/CPPS. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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Other

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10 pages, 1894 KiB  
Case Report
Tumor-Homing of Mesenchymal Stem Cells Infected with Oncolytic Virus in a Canine Patient
by Pablo Delgado-Bonet, Beatriz Davinia Tomeo-Martín, Gustavo Ortiz-Díez and Ana Judith Perisé-Barrios
Vet. Sci. 2022, 9(6), 285; https://doi.org/10.3390/vetsci9060285 - 9 Jun 2022
Cited by 3 | Viewed by 3034
Abstract
Intravenous administration of oncolytic adenovirus (OAds) can be challenging, although various vehicles for the delivery of the virus to the tumor have been described. The efficacy of mesenchymal stem cells (MSCs) as a virus vehicle has been reported in mouse models and canine [...] Read more.
Intravenous administration of oncolytic adenovirus (OAds) can be challenging, although various vehicles for the delivery of the virus to the tumor have been described. The efficacy of mesenchymal stem cells (MSCs) as a virus vehicle has been reported in mouse models and canine and human patients, but the actual action mechanism has never been described in patients. It is of importance to determine whether MSCs infected with OAds can reach the tumor and release the virus in a clinical setting. For this purpose, GFP-labeled MSCs were infected with an OAd and inoculated into a companion dog diagnosed with spontaneous lung carcinoma. Forty-eight hours later, the tumor was excised and analyzed microscopically by flow cytometry for GFP fluorescence detection, and a cellular culture was established. Peripheral blood samples were taken to quantify the oncolytic adenovirus by qRT-PCR. Green fluorescence cells detected in the cellular culture by microscopy and flow cytometry revealed 0.69% GFP-positive cells in the tumor. OAd in peripheral blood was confirmed by qRT-PCR during follow-up. For the first time, the tumoral-homing capacity of OAds infected-MSC has been confirmed in a clinical setting, helping to explain the clinical response mechanism, whose efficacy was previously reported in canine and human patients. Full article
(This article belongs to the Special Issue Animal and Disease Models in Biomedical Research)
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