Animal models are essential for investigating the pathogenesis and developing the treatment of human diseases. Identification of genetic mutations responsible for neurodegenerative diseases has enabled the creation of a large number of small animal models that mimic genetic defects found in the affected individuals. Of the current animal models, rodents with genetic modifications are the most commonly used animal models and provided important insights into pathogenesis. However, most of genetically modified rodent models lack overt neurodegeneration, imposing challenges and obstacles in utilizing them to rigorously test the therapeutic effects on neurodegeneration. Recent studies that used CRISPR/Cas9-targeted large animal (pigs and monkeys) have uncovered important pathological events that resemble neurodegeneration in the patient's brain but could not be produced in small animal models. Here we highlight the unique nature of large animals to model neurodegenerative diseases as well as the limitations and challenges in establishing large animal models of neurodegenerative diseases, with focus on Huntington disease, Amyotrophic lateral sclerosis, and Parkinson diseases. We also discuss how to use the important pathogenic insights from large animal models to make rodent models more capable of recapitulating important pathological features of neurodegenerative diseases.
Amyotrophic Lateral Sclerosis/genetics* ; Animals ; Brain/pathology* ; Disease Models, Animal ; Gene Editing ; Neurodegenerative Diseases/pathology* ; Swine

Objective: To explore the effect of deep dermal tissue dislocation injury on skin fibrosis in pig, in order to provide some theoretical basis for burn scar treatment. Methods: The experimental research method was applied. Six 2-month-old female Duroc pigs were taken. Fifteen operative areas on the right dorsum of pigs on which medium-thick skin grafts and deep dermal tissue slices were cut and re-implanted were included into dermal in situ reimplantation group, and fifteen operative areas on the left dorsum of pigs on which medium-thick skin grafts and deep dermal tissue slices were cut and the deep dermal tissue slice was placed under the fat layer were included into the dermal dislocation group. The hair growth in the operative areas on post-injury day (PID) 7, 14, and 21 and the cross-sectional structure on PID 14 were observed in the two groups. On PID 7, 14, and 21, the skin thickness (the distance from the epidermis to the upper edge of the fat), the dermal thickness (the distance from the lower edge of the epidermis to the upper edge of the fat, excluding the fibrotic tissue thickness between the dermis and the fat), and the fibrosis tissue thickness of the dermis-fat interface (from the lower edge of the deep dermis to the upper edge of the fat in dermal in situ reimplantation group and from the lower edge of the superficial dermis to the upper edge of the fat in dermal dislocation group) in the operative areas were measured and compared between the two groups; the fibrotic tissue thickness at the dermal cutting interface (from the lower edge of the superficial dermis to the upper edge of the deep dermis) in the operative areas in dermal in situ reimplantation group was measured and compared with the fibrotic tissue thickness at the dermal-fat interface. Sirius red staining was performed to observe and compare the type Ⅰ and Ⅲ collagen content in the dermal-fat interface in the operative areas between the 2 groups and between the dermal cutting interface and dermal-fat interface in the operative areas in dermal in situ reimplantation group. Immunohistochemical staining was performed to observe the positive expressions of proliferating cell nuclear antigen (PCNA), transforming growth factor β₁ (TGF-β₁), fibroblast growth factor 2 (FGF-2), and hepatocyte growth factor (HGF) in the operative areas in the two groups. The sample number was 6. Data were statistically analyzed with independent sample t test. Results: On PID 7, 14, and 21, the hairs in the operative areas in dermal in situ reimplantation group were denser than those in dermal dislocation group. On PID 14, the skin cross section in the operative areas in dermal dislocation group showed a "sandwich"-like structure, while the skin cross section in the operative areas in dermal in situ reimplantation group had normal structure. On PID 7, 14, and 21, the skin thickness in the operative areas in dermal dislocation group was (4 234±186), (4 688±360), and (4 548±360) μm, respectively, which was close to (4 425±156), (4 714±141), and (4 310±473) μm in dermal in situ reimplantation group (P>0.05); the dermal thickness in the operative areas in dermal dislocation group was significantly thinner than that in dermal in situ reimplantation group (with t values of -9.73, -15.85, and -15.41, respectively, P<0.01); the fibrotic tissue thickness at the dermal-fat interface in the operative areas in dermal dislocation group was significantly thicker than that in dermal in situ reimplantation group (with t values of 14.48, 20.58, and 15.67, respectively, P<0.01); there was no statistically significant difference between the fibrotic tissue thickness at the dermal-fat interface and the dermal cutting interface in the operative areas in dermal in situ reimplantation group (P>0.05). On PID 7, 14, 21, the type Ⅲ collagen content in the dermal-fat interface in the operative areas in dermal dislocation group was increased significantly compared with that in dermal in situ replantation group (with t values of 2.65, 0.61, and 7.39, respectively, P<0.05 or P<0.01), whereas there were no statistically significant differences in the type Ⅰ collagen content at the dermal-fat interface in the operative areas between the 2 groups (P>0.05) and the type Ⅰ and Ⅲ collagen content between the dermal-fat interface and the dermal cutting interface in the operative areas in dermal in situ reimplantation group (P>0.05). On PID 7, 14, and 21, PCNA, TGF-β₁, FGF-2, and HGF were positively expressed in the superficial dermis and adipose tissue in the operative areas in dermal dislocation group, while PCNA, TGF-β₁, FGF-2, and HGF were positively expressed in the superficial dermis, deep dermis, and adipose tissue in the operative areas in dermal in situ reimplantation group. Conclusions: Inadequate intrinsic thickness of dermal tissue is the key factor causing fibrosis, and the biological purpose of fibrosis is to "compensate" the intrinsic thickness of the skin. Besides, adipose tissue may also be an important component of fibrotic skin repair.
Swine ; Female ; Animals ; Dermis/pathology* ; Proliferating Cell Nuclear Antigen/metabolism* ; Fibroblast Growth Factor 2 ; Cross-Sectional Studies ; Fibrosis ; Skin Diseases/pathology* ; Collagen/metabolism*

To reduce swine production costs, a slaughter check system has been developed in countries with an advanced swine industry. Evaluation of lung lesions in carcasses is a critical part of the slaughter check system. This study was performed to collect background information for use in developing a slaughter check system in Korea. Lung tissues and their gross images were collected from slaughterhouses in Gyeonggi-do, Korea. Scoring of the gross lung lesions was performed on the lung images. Histopathologic examination was conducted to classify the pulmonary lesions as bronchopneumonia or interstitial pneumonia. Scores of the gross lung lesions were significantly different between bronchopneumonia and interstitial pneumonia groups (p < 0.001). A 90% confidence interval of gross lung lesion scores was established for the bronchopneumonia group, and the lesion scoring had a sensitivity of 100% and specificity of 77.3%. The gross lung lesion scoring test was subjected to a diagnostic distinction evaluation by examining the receiver operating characteristic curve and was appraised as having good discrimination for bronchopneumonia. Establishment of a gross lung lesion scoring test for the diagnosis of bronchopneumonia could be valuable as a screening test of macroscopic bronchopneumonia in swine slaughter check system.
Abattoirs* ; Bronchopneumonia ; Diagnosis* ; Discrimination (Psychology) ; Gyeonggi-do ; Korea ; Lung Diseases, Interstitial ; Lung* ; Mass Screening ; Pathology ; Pneumonia* ; ROC Curve ; Sensitivity and Specificity ; Swine*

BACKGROUND AND OBJECTIVES: Thoracic endovascular aortic repair exhibits limitations in cases where the aortic pathology involves the aortic arch. We had already developed a fenestrated aortic stent graft (FASG) with a preloaded catheter for aortic pathology involving the aortic arch. FASG was suitable for elective cases. MATERIALS AND METHODS: An aortic arch stent graft with a window-shaped fenestration (FASG-W) for supra-aortic arch vessels is suitable for emergent cases. This study aims to test a FASG-W for supra-aortic arch vessels and to perform a preclinical study in swine to evaluate the safety and efficacy of this device. Six FASG-Ws with 1 preloaded catheter were advanced through the iliac artery in 6 swine. The presence of endoleak and the patency and deformity of the grafts were examined with computed tomography (CT) at 4 weeks postoperatively. A postmortem examination was performed at 8 weeks. The mean procedure time for FASG-W was 27.15±4.02 minutes. The mean time for the selection of the right carotid artery was 5.72±0.72 minutes. RESULTS: Major adverse events were not observed in any of the 6 pigs who survived for 8 weeks. For the FASG-W, no endoleaks, no disconnection, and no occlusion of the stent grafts were observed in the CT findings or the postmortem gross findings. CONCLUSION: The procedure with the FASG-W was able to be performed safely in a relatively short procedure time and involved an easy technique. The FASG-W was found to be safe and convenient for use in this preclinical study of swine.
Animal Experimentation ; Aorta, Thoracic* ; Aortic Aneurysm, Thoracic ; Aortic Diseases ; Autopsy ; Blood Vessel Prosthesis* ; Carotid Arteries ; Catheters ; Congenital Abnormalities ; Endoleak ; Iliac Artery ; Pathology ; Stents* ; Swine* ; Transplants

Toxoplasma gondii is a protozoan parasite with a broad range of intermediate hosts. Chickens as important food-producing animals can also serve as intermediate hosts. To date, experimental studies on the pathogenicity of T. gondii in broiler chickens were rarely reported. The objective of the present study was to compare the pathogenicity of 5 different T. gondii strains (RH, CN, JS, CAT2, and CAT3) from various host species origin in 10-day-old chickens. Each group of chickens was infected intraperitoneally with 5 x 10(8), 1 x 10(8), 1 x 10(7), and 1 x 10(6) tachyzoites of the 5 strains, respectively. The negative control group was mockly inoculated with PBS alone. After infection, clinical symptoms and rectal temperatures of all the chickens were checked daily. Dead chickens during acute phage of the infection were checked for T. gondii tachyzoites by microscope, while living cases were checked for T. gondii infection at day 53 post-inoculation (PI) by PCR method. Histopathological sections were used to observe the pathological changes in the dead chickens and the living animals at day 53 PI. No significant differences were found in survival periods, histopathological findings, and clinical symptoms among the chickens infected with the RH, CN, CAT2, and CAT3 strains. Histopathological findings and clinical symptoms of the JS (chicken origin) group were similar to the others. However, average survival times of infected chickens of the JS group inoculated with 5 x 10(8) and 1 x 10(8) tachyzoites were 30.0 and 188.4 hr, respectively, significantly shorter than those of the other 4 mammalian isolates. Chickens exposed to 10(8) of T. gondii tachyzoites and higher showed acute signs of toxoplasmosis, and the lesions were relatively more severe than those exposed to lower doses. The results indicated that the pathogenicity of JS strain was comparatively stronger to the chicken, and the pathogenicity was dose-dependent.
Animals ; Antibodies, Protozoan/blood ; Cat Diseases/parasitology ; Cats ; Chickens ; Poultry Diseases/blood/mortality/*parasitology/pathology ; Swine ; Swine Diseases/parasitology ; Toxoplasma/genetics/growth & development/*pathogenicity/physiology ; Toxoplasmosis, Animal/blood/mortality/*parasitology/pathology ; Virulence

OBJECTIVETo establish a miniature pig model of mandibular osteoradionecrosis (ORN).

METHODSA single dose of irradiation (IR25 Gy, 28 Gy) was delivered via an electronic linear accelerator to the right mandible of 24 miniature pigs by utilizing three dimensional conformal radiotherapy (3D-CRT). The first molar of the mandible was extracted 2 months after radiation. Mandibular ORN was diagnosed through gross observation, X-ray film, CT, and histopathologic examination.

RESULTSAt 3-4 months after radiation, all animals suffered from mandibular ORN after dental extraction. The symptoms of ORN were more severe in the 28 Gy group than in the 25 Gy group.

CONCLUSIONA miniature pig model of mandibular ORN can be established through 25 Gy irradiation + dental extraction.

Animals ; Mandible ; Mandibular Diseases ; pathology ; Molar ; Osteoradionecrosis ; pathology ; Particle Accelerators ; Radiation Injuries, Experimental ; pathology ; Radiotherapy, Conformal ; adverse effects ; Swine ; Swine, Miniature ; Tooth Extraction

Somatic cell nuclear transfer (SCNT) is a cost-effective technique for producing transgenic pigs. However, abnormalities in the cloned pigs might prevent use these animals for clinical applications or disease modeling. In the present study, we generated several cloned pigs. One of the pigs was found to have intrapancreatic ectopic splenic tissue during histopathology analysis although this animal was grossly normal and genetically identical to the other cloned pigs. Ectopic splenic tissue in the pancreas is very rare, especially in animals. To the best of our knowledge, this is the first such report for cloned pigs.
Animals ; Animals, Genetically Modified ; Choristoma/pathology/*veterinary ; Cloning, Organism ; Nuclear Transfer Techniques/*veterinary ; *Pancreas ; Splenic Diseases/pathology/*veterinary ; Swine ; Swine Diseases/*pathology ; Swine, Miniature

Wnt proteins are a family of secreted glycoproteins that are evolutionarily conserved and considered to be involved in extensive developmental processes in metazoan organisms. The characterization of wnt genes may improve understanding the parasite's development. In the present study, a wnt4 gene encoding 491amino acids was amplified from cDNA of metacestodes of Taenia solium using reverse transcription PCR (RT-PCR). Bioinformatics tools were used for sequence analysis. The conserved domain of the wnt gene family was predicted. The expression profile of Wnt4 was investigated using real-time PCR. Wnt4 expression was found to be dramatically increased in scolex evaginated cysticerci when compared to invaginated cysticerci. In situ hybridization showed that wnt4 gene was distributed in the posterior end of the worm along the primary body axis in evaginated cysticerci. These findings indicated that wnt4 may take part in the process of cysticerci evagination and play a role in scolex/bladder development of cysticerci of T. solium.
Animals ; Base Sequence ; Cysticercosis/pathology ; Cysticercus/enzymology/*genetics ; DNA, Helminth/*genetics ; Gene Expression Regulation ; Humans ; In Situ Hybridization ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sus scrofa ; Swine ; Swine Diseases ; Taenia solium/embryology/enzymology/*genetics ; Wnt4 Protein/*genetics

Our investigation was conducted in order to verify a recent severe epidemic at several swine farms in northern China that indicated a newly emerging disease. Evidence confirmed that the epidemic was caused by a virulent Pseudorabies virus infection in swine herds.
Animals ; China/epidemiology ; Enzyme-Linked Immunosorbent Assay/veterinary ; Epidemics/*veterinary ; Herpesvirus 1, Suid/classification/*isolation & purification/*pathogenicity ; Pseudorabies/*epidemiology/mortality/pathology/virology ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Sequence Analysis, DNA/veterinary ; Swine ; Swine Diseases/*epidemiology/mortality/pathology/virology ; Vaccination/adverse effects/veterinary ; Virulence

The aim of this study was to evaluate the presence of Helicobacter (H.) spp. in swine affected by gastric ulceration. Stomachs from 400 regularly slaughtered swine were subjected to gross pathological examination to evaluate the presence of gastric ulcers. Sixty-five samples collected from ulcerated pars esophagea and 15 samples from non-ulcerated pyloric portions were submitted to histopathological and molecular analyses, to detect Helicobacter spp., H. suis and H. pylori by PCR. Feces and saliva swabs were also collected from 25 animals in order to detect in vivo the presence of Helicobacter spp.. Gastric ulcers were detected in 373 cases (93%). The presence of ulcers in association with inflammatory processes was further confirmed by histological examination. Forty-nine percent (32/65) of the ulcerated esophageal portions as well as 53% (8/15) of the non-ulcerated pyloric portions were positive for Helicobacter spp. by PCR. The Helicobacter spp. positive samples were also positive for H. suis, while H. pylori was not detected. These results were confirmed by restriction enzyme analysis. With regard to feces and saliva samples, 15/25 (60%) and 16/25 (64%) were positive for Helicobacter spp. PCR, respectively but all were negative in H. suis and H. pylori specific PCR.
Animals ; Feces/*microbiology ; Helicobacter/*isolation & purification ; Polymerase Chain Reaction/veterinary ; Restriction Mapping/veterinary ; Saliva/*microbiology ; Stomach/*microbiology ; Stomach Ulcer/microbiology/pathology/*veterinary ; Swine ; Swine Diseases/*microbiology/pathology