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Biology
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Applications of the Goat Model in Biomedical Research
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Applications of the Goat Model in Biomedical Research

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (29 December 2022) | Viewed by 27915

Special Issue Editor

Dr. Isabel R. Dias

E-Mail Website
Guest Editor
Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
Interests: small animal surgery; animal models for orthopedic research; bone turnover markers; fracture healing process; bone and chondral tissue engineering and regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Small ruminants are recognized animal models for preclinical and translational studies to humans in biomedical research. They have the great advantage of being cooperative and compliance, easily available, handle and housed, and relatively low cost. They also do not require excessive care in their feeding, housing and sanitary prophylaxis. Their physical stature and weight allows to conduct biomedical research in more realistic clinical situations. They are livestock species, so their use in experimental research is relatively well accepted by the general society.

Sheep has been widely used for biomedical research purposes, resulting these studies in numerous scientific articles and very recent reviews, comparatively the goat remains largely unexplored in terms of scientific publications. In this way, the idea of creating a special issue of Biology journal that compiles main research studies in the biomedical area in which the goat model can be used arises.

Thus, we invite the submission of original articles and reviews in biomedical research using the goat model, namely for the study of human diseases (chronic rheumatoid arthritis, congenital myotonia, cardiovascular conditions like atrial fibrillation, Q fever), as antibody producer (immunological research, immunotherapy, diagnosis), orthopedic, reproduction and cancer research, genome engineering for production of pharmaceutical proteins, generation of models of human diseases and hosts for the growth of human organs, among other fields.

Dr. Isabel R. Dias
Guest Editor

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Keywords

  • goat, animal model
  • human diseases
  • biomedical research
  • testing

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Published Papers (8 papers)

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Research

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11 pages, 3031 KiB  
Article
The Contribution of the Sheep and the Goat Model to the Study of Ovarian Ageing
by Luís Montenegro, Paulo Magalhães, Adriana Costa Guerreiro, Catarina Brandão, Anabela Pinto, Henrique Almeida, Ana Martins-Bessa and Elisabete Silva
Biology 2023, 12(2), 270; https://doi.org/10.3390/biology12020270 - 8 Feb 2023
Viewed by 2908
Abstract
Ovarian ageing stands as the major contributor towards fertility loss. As such, there is an urge for studies addressing the mechanisms that promote ovarian ageing and new strategies aiming to delay it. Recently, the presence of a unique population of multinucleated giant cells [...] Read more.
Ovarian ageing stands as the major contributor towards fertility loss. As such, there is an urge for studies addressing the mechanisms that promote ovarian ageing and new strategies aiming to delay it. Recently, the presence of a unique population of multinucleated giant cells has been identified in the ovaries of reproductively aged mice. These cells have been considered hallmarks of ovarian ageing. However, up to date multinucleated giant cells have only been described in the ovaries of the mice. Therefore, the aim of the present work was to evaluate and characterize the presence of such hallmarks of ovarian ageing in the sheep and the goat. In this study, ovaries from juvenile (6 months) and mature animals (18–24 months) were used. The hematoxylin and eosin technique was performed to describe the ovarian morphology and evaluate the ovarian follicle reserve pool. Sudan black B staining and the detection of autofluorescence emission were used to identify and characterize the presence of multinucleated giant cells. Statistical analyses were performed with GraphPad Prism 9.0.0. A decrease in the follicle reserve pool and the presence of multinucleated giant cells, with lipofuscin accumulation and the emission of autofluorescence, were observed in the ovaries of the mature animals of both species. Our results support the interest in the use of the ovine and the caprine model, that share physiological and pathophysiological characteristics with humans, in future studies addressing ovarian ageing. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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9 pages, 3417 KiB  
Article
Goats as Valuable Animal Model to Test the Targeted Glutamate Supplementation upon Antral Follicle Number, Ovulation Rate, and LH-Pulsatility
by Luis A. Luna-García, César A. Meza-Herrera, Carlos C. Pérez-Marín, Rebeca Corona, Juan R. Luna-Orozco, Francisco G. Véliz-Deras, Ramón Delgado-Gonzalez, Rafael Rodriguez-Venegas, Cesar A. Rosales-Nieto, Jorge A. Bustamante-Andrade and Ulises N. Gutierrez-Guzman
Biology 2022, 11(7), 1015; https://doi.org/10.3390/biology11071015 - 6 Jul 2022
Cited by 4 | Viewed by 2043
Abstract
The potential effect of intravenous administration of glutamate on the ovarian activity and the LH secretion pattern, considering the anestrous yearling goat as an animal model, were assessed. In late April, yearling goats (n = 20) were randomly assigned to either (1) [...] Read more.
The potential effect of intravenous administration of glutamate on the ovarian activity and the LH secretion pattern, considering the anestrous yearling goat as an animal model, were assessed. In late April, yearling goats (n = 20) were randomly assigned to either (1) Glutamate supplemented (GLUT; n = 10, Live Weight (LW) = 29.6 ± 1.02 kg, Body Condition (BCS) = 3.4 ± 0.2 units; i.v. supplemented with 7 mg GLUT kg−1 LW) or (2) Non-supplemented (CONT; n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2 units; i.v. saline). The oats were estrus-synchronized; blood sampling (6 h × 15 min) was carried out for LH quantification. Response variables included pulsatility (PULSE), time to first pulse (TTFP), amplitude (AMPL), nadir (NAD), and area under the curve (AUC) of LH. Ovaries were ultra-sonographically scanned to assess ovulation rate (OR), number of antral follicles (AF), and total ovarian activity (TOA = OR + AF). LH-PULSE was quantified with the Munro algorithm; significant treatment x time interactions were evaluated across time. The variables LW and BCS did not differ (p > 0.05) between the experimental groups. Nevertheless, OR (1.77 vs. 0.87 ± 0.20 units), TOA (4.11 vs. 1.87 ± 0.47 units) and LH-PULSE (5.0 vs. 2.2 pulses 6 h-1) favored (p < 0.05) to the GLUT group. Our results reveal that targeted glutamate supplementation, the main central nervous system neurotransmitter, arose as an interesting strategy to enhance the hypothalamic–hypophyseal–ovarian response considering the anestrous-yearling goat as an animal model, with thought-provoking while promising translational applications. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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18 pages, 9250 KiB  
Article
Osteosynthesis Metal Plate System for Bone Fixation Using Bicortical Screws: Numerical–Experimental Characterization
by Andrea A. R. Olmos, Aureliano Fertuzinhos, Teresa D. Campos, Isabel R. Dias, Carlos A. Viegas, Fábio A. M. Pereira, Nguyễn T. Quyền, Marcelo F. S. F. de Moura, Andrea Zille and Nuno Dourado
Biology 2022, 11(6), 940; https://doi.org/10.3390/biology11060940 - 20 Jun 2022
Cited by 2 | Viewed by 2586
Abstract
This study reports the numerical and experimental characterization of a standard immobilization system currently being used to treat simple oblique bone fractures of femoral diaphyses. The procedure focuses on the assessment of the mechanical behavior of a bone stabilized with a dynamic compression [...] Read more.
This study reports the numerical and experimental characterization of a standard immobilization system currently being used to treat simple oblique bone fractures of femoral diaphyses. The procedure focuses on the assessment of the mechanical behavior of a bone stabilized with a dynamic compression plate (DCP) in a neutralization function, associated to a lag screw, fastened with surgical screws. The non-linear behavior of cortical bone tissue was revealed through four-point bending tests, from which damage initiation and propagation occurred. Since screw loosening was visible during the loading process, damage parameters were measured experimentally in independent pull-out tests. A realistic numerical model of the DCP-femur setup was constructed, combining the evaluated damage parameters and contact pairs. A mixed-mode (I+II) trapezoidal damage law was employed to mimic the mechanical behavior of both the screw–bone interface and bone fractures. The numerical model replicated the global behavior observed experimentally, which was visible by the initial stiffness and the ability to preview the first loading peak, and bone crack satisfactorily. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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13 pages, 1394 KiB  
Article
Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs
by Maaike K. van Gelder, Jasper Stevens, Tobias T. Pieters, Koen R. D. Vaessen, Jaap A. Joles, Marianne C. Verhaar and Karin G. F. Gerritsen
Biology 2021, 10(6), 461; https://doi.org/10.3390/biology10060461 - 23 May 2021
Cited by 3 | Viewed by 2663
Abstract
The preclinical evaluation of novel therapies for chronic kidney disease requires a simple method for the assessment of kidney function in a uremic large animal model. An intravenous bolus of iohexol was administered to goats (13 measurements in n = 3 goats) and [...] Read more.
The preclinical evaluation of novel therapies for chronic kidney disease requires a simple method for the assessment of kidney function in a uremic large animal model. An intravenous bolus of iohexol was administered to goats (13 measurements in n = 3 goats) and pigs (23 measurements in n = 5 pigs) before and after induction of kidney failure, followed by frequent blood sampling up to 1440 min. Plasma clearance (CL) was estimated by a nonlinear mixed-effects model (CLNLME) and by a one-compartmental pharmacokinetic disposition model using iohexol plasma concentrations during the terminal elimination phase (CL1CMT). A simple method (CLSM) for the calculation of plasma clearance was developed based on the most appropriate relationship between CLNLME and CL1CMT. CLSM and CLNLME showed good agreement (CLNLME/CLSM ratio: 1.00 ± 0.07; bias: 0.03 ± 1.64 mL/min; precision CLSM and CLNLME: 80.9% and 80.7%, respectively; the percentage of CLSM estimates falling within ±30% (P30) or ±10% (P10) of CLNLME: 53% and 12%, respectively). For mGFRNLME vs. mGFRSM, bias was −0.25 ± 2.24 and precision was 49.2% and 53.6%, respectively, P30 and P10 for mGFR based on CLSM were 71% and 24%, respectively. A simple method for measurement of GFR in healthy and uremic goats and pigs was successfully developed, which eliminates the need for continuous infusion of an exogenous marker, urine collection and frequent blood sampling. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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16 pages, 1589 KiB  
Article
A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin
by Maaike K. van Gelder, Joost C. de Vries, Sabbir Ahmed, Anneke S. Monninkhof, Gérard A. P. de Kort, Evert-Jan P. A. Vonken, Diënty H. M. Hazenbrink, Koen R. D. Vaessen, Tri Q. Nguyen, Marianne C. Verhaar, Jaap A. Joles and Karin G. F. Gerritsen
Biology 2021, 10(4), 292; https://doi.org/10.3390/biology10040292 - 3 Apr 2021
Cited by 4 | Viewed by 3131
Abstract
A large animal model of (end-stage) kidney disease (ESKD) is needed for the preclinical testing of novel renal replacement therapies. This study aimed to create stable uremia via subtotal renal artery embolization in goats and induce a temporary further decline in kidney function [...] Read more.
A large animal model of (end-stage) kidney disease (ESKD) is needed for the preclinical testing of novel renal replacement therapies. This study aimed to create stable uremia via subtotal renal artery embolization in goats and induce a temporary further decline in kidney function by administration of gentamicin. Renal artery embolization was performed in five Dutch white goats by infusing polyvinyl alcohol particles in branches of the renal artery, aiming for the embolization of ~80% of one kidney and complete embolization of the contralateral kidney. Gentamicin was administered to temporarily further increase the plasma concentrations of uremic toxins. After initial acute kidney injury, urea and creatinine plasma concentrations stabilized 1.5 ± 0.7 months post-embolization and remained elevated (12 ± 1.4 vs. 5.6 ± 0.8 mmol/L and 174 ± 45 vs. 65 ± 5.6 µmol/L, resp.) during follow-up (16 ± 6 months). Gentamicin induced temporary acute-on-chronic kidney injury with a variable increase in plasma concentrations of small solutes (urea 29 ± 15 mmol/L, creatinine 841 ± 584 µmol/L, phosphate 2.2 ± 0.3 mmol/L and potassium 5.0 ± 0.6 mmol/L) and protein-bound uremic toxins representative of patients with ESKD. A uremic goat model characterized by stable moderate uremia was established via subtotal renal artery embolization with the induction of temporary severe acute-on-chronic kidney injury by the administration of gentamicin, allowing preclinical in vivo validation of novel renal replacement technologies. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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Review

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19 pages, 1777 KiB  
Review
Role of Goats in the Epidemiology of Coxiella burnetii
by Sofia Anastácio, Sérgio Ramalho de Sousa, Maria José Saavedra and Gabriela Jorge da Silva
Biology 2022, 11(12), 1703; https://doi.org/10.3390/biology11121703 - 25 Nov 2022
Cited by 8 | Viewed by 3428
Abstract
Since its first description in the late 1930s, Q fever has raised many questions. Coxiella burnetii, the causative agent, is a zoonotic pathogen affecting a wide range of hosts. This airborne organism leads to an obligate, intracellular lifecycle, during which it multiplies [...] Read more.
Since its first description in the late 1930s, Q fever has raised many questions. Coxiella burnetii, the causative agent, is a zoonotic pathogen affecting a wide range of hosts. This airborne organism leads to an obligate, intracellular lifecycle, during which it multiplies in the mononuclear cells of the immune system and in the trophoblasts of the placenta in pregnant females. Although some issues about C. burnetii and its pathogenesis in animals remain unclear, over the years, some experimental studies on Q fever have been conducted in goats given their excretion pattern. Goats play an important role in the epidemiology and economics of C. burnetii infections, also being the focus of several epidemiological studies. Additionally, variants of the agent implicated in human long-term disease have been found circulating in goats. The purpose of this review is to summarize the latest research on C. burnetii infection and the role played by goats in the transmission of the infection to humans. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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22 pages, 658 KiB  
Review
Mesenchymal Stem Cell Studies in the Goat Model for Biomedical Research—A Review of the Scientific Literature
by Inês E. Dias, Carlos A. Viegas, João F. Requicha, Maria J. Saavedra, Jorge M. Azevedo, Pedro P. Carvalho and Isabel R. Dias
Biology 2022, 11(9), 1276; https://doi.org/10.3390/biology11091276 - 27 Aug 2022
Cited by 7 | Viewed by 3529
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells, defined by their ability to self-renew, while maintaining the capacity to differentiate into different cellular lineages, presumably from their own germinal layer. MSCs therapy is based on its anti-inflammatory, immunomodulatory, and regenerative potential. Firstly, they can [...] Read more.
Mesenchymal stem cells (MSCs) are multipotent cells, defined by their ability to self-renew, while maintaining the capacity to differentiate into different cellular lineages, presumably from their own germinal layer. MSCs therapy is based on its anti-inflammatory, immunomodulatory, and regenerative potential. Firstly, they can differentiate into the target cell type, allowing them to regenerate the damaged area. Secondly, they have a great immunomodulatory capacity through paracrine effects (by secreting several cytokines and growth factors to adjacent cells) and by cell-to-cell contact, leading to vascularization, cellular proliferation in wounded tissues, and reducing inflammation. Currently, MSCs are being widely investigated for numerous tissue engineering and regenerative medicine applications. Appropriate animal models are crucial for the development and evaluation of regenerative medicine-based treatments and eventual treatments for debilitating diseases with the hope of application in upcoming human clinical trials. Here, we summarize the latest research focused on studying the biological and therapeutic potential of MSCs in the goat model, namely in the fields of orthopedics, dermatology, ophthalmology, dentistry, pneumology, cardiology, and urology fields. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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21 pages, 1021 KiB  
Review
Small Ruminants and Its Use in Regenerative Medicine: Recent Works and Future Perspectives
by Rui Damásio Alvites, Mariana Vieira Branquinho, Ana Catarina Sousa, Bruna Lopes, Patrícia Sousa, Carla Mendonça, Luís Miguel Atayde and Ana Colette Maurício
Biology 2021, 10(3), 249; https://doi.org/10.3390/biology10030249 - 22 Mar 2021
Cited by 22 | Viewed by 5150
Abstract
Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among [...] Read more.
Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions, larger than conventional laboratory animals, but very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with a focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research. Full article
(This article belongs to the Special Issue Applications of the Goat Model in Biomedical Research)
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