Veterinary Research最新文献

{"title":"Cell deconvolution-based integrated time-series network of whole blood transcriptome reveals systemic antiviral activities and cell-specific immunological changes against PRRSV infection.","authors":"Byeonghwi Lim, Chiwoong Lim, Min-Jae Jang, Young-Jun Seo, Do-Young Kim, Christopher K Tuggle, Kyu-Sang Lim, Jun-Mo Kim","doi":"10.1186/s13567-025-01451-w","DOIUrl":"10.1186/s13567-025-01451-w","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses in the swine industry. However, the molecular mechanisms behind the common and cell type-specific systemic responses during PRRS virus (PRRSV) infection are not well understood. In this study, we collected viremia data, antibody levels, and whole-blood RNA-seq data obtained from eight PRRSV-infected piglets. We utilised a cell deconvolution approach to calculate cell type enrichment, constructed a time-serial gene co-expression network with differentially expressed genes, and conducted functional annotations. Three significant modules were identified within the network. The changes associated with viremia revealed an upregulated expression of genes related to antiviral activity. In the T-cell- and NK-cell-specific modules, infection led to an increased T-cell population and upregulation of genes related to T-cell defence responses. Conversely, in the monocyte- and neutrophil-specific module, genes involved in inflammatory responses were downregulated due to a decrease in monocyte proportion. This study highlights the time-series antiviral activities associated with viremia and the transcriptomic changes associated with immune responses in specific cell types. The findings provide comprehensive insights into host responses to PRRSV infection, including diagnostic biomarkers.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"19"},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of sodium alginate hydrogel containing bacteriophage peptides that specifically bind to the EtCab protein on the inhibition of Eimeria tenella infection.","authors":"Hang Chen, Wenjing Zhi, Bingrong Bai, Faisal R Anjum, Zhipeng Jia, Rui Kong, Qiuju Liu, Biao Wang, Chunli Ma, Dexing Ma","doi":"10.1186/s13567-024-01425-4","DOIUrl":"10.1186/s13567-024-01425-4","url":null,"abstract":"<p><p>Avian coccidiosis, caused by the protozoan Eimeria, leads to significant economic losses for the poultry industry. In this study, bacteriophages that specifically bind to the calcium-binding protein (EtCab) of Eimeria tenella were selected using a biopanning process with a pIII phage display library. The recombinant EtCab protein served as the ligand in this selection process. The binding ability of target phages to the EtCab protein or E. tenella sporozoites was evaluated. The role of peptides corresponding to target phages in inhibiting the invasion of E. tenella sporozoites into cells was analysed using flow cytometry. Subsequently, the phages were encapsulated in sodium alginate to protect them from degradation in gastric fluid, which has a low pH value. Chickens were orally administered both microencapsulated and non-microencapsulated phages, and the protective effects against E. tenella infection were assessed. The binding mechanism of these peptides to the EtCab protein was investigated through in silico analysis. The results indicated that three specific phages (Y, G, and V) could bind effectively to recombinant EtCab protein as well as to sporozoite proteins. All three peptides, particularly Y and G, demonstrated significant inhibition of sporozoite invasion into cells in vitro. Additionally, oral administration of the encapsulated phages Y and G provided a higher level of protection against Eimeria infection compared to encapsulated phage V and the unencapsulated phages. Molecular docking studies revealed that three peptides, particularly Y and G, efficiently bind to the EtCab protein through hydrogen bonds. This study provides a reference for developing small molecular drugs targeting coccidiosis.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"18"},"PeriodicalIF":3.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRV-1b and PRV-3a infection is associated with the same clinical disease in coho salmon (Oncorhynchus kisutch) farmed in Chile: unraveling the pathogenesis of the orthoreoviral cardiomyopathy and hemolytic jaundice (OCHJ).","authors":"Marco Rozas-Serri, Ricardo Ildefonso, Andrea Peña, Victoria Jaramillo, Rodolfo Correa, Soraya Barrientos, Ariel Muñoz, Lucerina Maldonado, Estefanía Peñaloza","doi":"10.1186/s13567-024-01435-2","DOIUrl":"10.1186/s13567-024-01435-2","url":null,"abstract":"<p><p>Piscine orthoreovirus (PRV) is a virus that is widely distributed among global aquaculture populations of salmonid species. The coho salmon (Oncorhynchus kisutch) is a species of increasing productive and economic importance in Chile. The presence of PRV has generated concern about its impact on the health and welfare of this species. The objective of this study was to comparatively describe the clinical manifestations, pathological changes, and pathogenesis associated with PRV infection in two different farms of farmed coho salmon in Chile through a prospective longitudinal descriptive observational study. The results demonstrated that PRV-1b and PRV-3a are independently associated with the same clinical and pathological presentation in farmed coho salmon. Microscopic pathology of the disease associated with PRV-1b and PRV-3a was primarily characterized by degenerative and inflammatory findings in the heart and liver. Hematological and blood biochemistry biomarkers in fish exhibited alterations, manifesting as hemolytic anemia and prehepatic jaundice likely due to indirect hyperbilirubinemia. Pathogenesis of infection associated with both PRV-1b and PRV-3a would indicate a specific tropism for erythrocytes and cardiomyocytes of the spongy myocardium. It is noteworthy that despite a notable reduction in viral load of both PRV subgroups in tissues, the frequency of macroscopic lesions increased during the final phase of the study. In conclusion, the results indicate a strong correlation between infection by both PRV subgroups and the proposed orthoreoviral cardiomyopathy and hemolytic jaundice (OCHJ) disease. Further research on the pathogenesis and surveillance of PRV-1b and PRV-3a subgroups is pivotal to develop effective strategies for the control of OCHJ in farmed coho salmon.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"17"},"PeriodicalIF":3.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalein inhibits PRRSV through direct binding, targeting EGFR, and enhancing immune response.","authors":"Jing Wu, Qi Lu, Jing Hou, Yueqin Qiu, Min Tian, Li Wang, Kaiguo Gao, Xuefen Yang, Zongyong Jiang","doi":"10.1186/s13567-024-01440-5","DOIUrl":"10.1186/s13567-024-01440-5","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) presents significant economic challenges to the global pork industry due to its ability to mutate rapidly. The current commercial vaccines have limited effectiveness, and there are strict restrictions on the use of antiviral chemical drugs. Therefore, it is urgent to identify new strategies for preventing and controlling PRRSV infections. Baicalein, a flavonoid derived from Scutellaria baicalensis, has gained attention for its potential antiviral properties. However, there is little information about the effects and mechanisms of baicalein in relation to PRRSV. In this study, a network pharmacology analysis identified seven potential targets of baicalein against PRRSV, with the epidermal growth factor receptor (EGFR) emerging as the core target. The results of molecular docking and dynamics (MD) simulations confirmed that baicalein has a high binding affinity for EGFR, with a measured value of - 7.935 kcal/mol. Additionally, both in vitro (EC₅₀ = 10.20 μg/mL) and in vivo (2.41 mg/kg) experiments were conducted to assess the effectiveness of baicalein against PRRSV. Notably, baicalein was found to inhibit various stages of the PRRSV replication cycle and could directly bind to PRRSV in vitro. Baicalein inhibited the entry of PRRSV by blocking EGFR phosphorylation and the downstream PI3K-AKT signaling pathway. This was confirmed by a decrease in the expression of p-EGFR/EGFR, p-AKT/AKT, PI3K, and SRC following treatment with baicalein. Additionally, baicalein significantly enhanced the immune response in piglets infected with PRRSV. In conclusion, this study suggests that baicalein may be a promising pharmaceutical candidate for preventing and controlling PRRS, offering new insights into the antiviral potential of Chinese herbal medicine.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"16"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deltacoronavirus HKU11, HKU13, PDCoV (HKU15) and HKU17 spike pseudoviruses enter avian DF-1 cells via clathrin-mediated endocytosis in a Rab5-, Rab7- and pH-dependent manner.","authors":"Qi-Zhang Liang, Chun-Miao Ji, Bin Wang, Wei Chen, Feng Cong, Yu Huang, Yao-Wei Huang","doi":"10.1186/s13567-024-01442-3","DOIUrl":"https://doi.org/10.1186/s13567-024-01442-3","url":null,"abstract":"<p><p>Porcine deltacoronavirus (PDCoV), also known as HKU15, is a swine enteropathogenic virus that is believed to have originated in birds. PDCoV belongs to the genus Deltacoronavirus (DCoV), the members of which have mostly been identified in diverse avian species. We recently reported that chicken or porcine aminopeptidase N (APN), the major cellular receptor for PDCoV, can mediate cellular entry via three pseudotyped retroviruses displaying spike proteins from three avian DCoVs (HKU11, HKU13, and HKU17). In the present work, to better understand how avian-origin CoVs may be transmitted to pigs, we investigated the unknown DCoV entry pathway in avian cells. We show that clathrin-mediated endocytosis is involved in the entry of these DCoV pseudoviruses into chicken-origin DF-1 cells. Pseudovirus entry was suppressed by means of pharmacological inhibitors, dominant-negative mutants, and siRNAs targeting various cellular proteins and signalling molecules, suggesting that PDCoV and avian DCoV pseudovirus entry into DF-1 cells depends on clathrin, dynamin-2, cathepsins and a low-pH environment but is independent of caveolae and macropinocytosis. Furthermore, we found that DCoV pseudovirus entry was linked to Rab5- and Rab7-dependent pathways. This is the first report demonstrating that these DCoVs utilize clathrin-mediated endocytosis pathways to enter avian-origin cells, providing new insights into interspecies transmission of DCoVs.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"15"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM8 inhibits porcine epidemic diarrhoea virus replication by targeting and ubiquitinately degrading the nucleocapsid protein.","authors":"Zhenbin Bi, Wei Wang, Shanshen Gu, Yajing Zhou, Zhengchang Wu, Wenbin Bao, Haifei Wang","doi":"10.1186/s13567-024-01443-2","DOIUrl":"https://doi.org/10.1186/s13567-024-01443-2","url":null,"abstract":"<p><p>Porcine epidemic diarrhoea virus (PEDV) is an enteric pathogen that causes acute diarrhoea, dehydration and high mortality rates in suckling pigs. Tripartite motif 8 (TRIM8) has been shown to play multiple roles in the host's defence against viral infections. However, the functions of TRIM8 in regulating PEDV infection are still not well understood. In our study, we found a significant upregulation of TRIM8 following PEDV infection. We created TRIM8 knockout and overexpression cell lines and discovered that TRIM8 can inhibit PEDV replication within host cells. Co-immunoprecipitation assays revealed that TRIM8 directly interacts with the nucleocapsid protein (N) of PEDV, specifically within the coiled-coil structural domain of TRIM8. Furthermore, TRIM8 was shown to reduce the expression of the PEDV N protein in a dose-dependent manner. Mechanistically, TRIM8 inhibits the expression of PEDV N through K48-linked ubiquitin proteasome degradation. Transcriptomics analysis revealed that TRIM8 facilitates the expression of genes associated with several pathways, including the IL-17 signalling pathway, chemokine signalling pathway, and cytokine-cytokine receptor interaction. This suggests that TRIM8 plays a crucial role in boosting antiviral immune responses against PEDV infection. Our findings provide new insights into the functions and mechanisms of TRIM8 in regulating PEDV infection and highlight its potential as a molecular target for the prevention and control of this virus.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"14"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly identified c-di-GMP pathway putative EAL domain gene STM0343 regulates stress resistance and virulence in Salmonella enterica serovar Typhimurium.","authors":"Kaifeng Chen, Lili Li, Nanwei Wang, Zhouping Zhou, Peng Pan, Chenggang Xu, Dage Sun, Jiayi Li, Changzhi Dai, Dai Kuang, Ming Liao, Jianmin Zhang","doi":"10.1186/s13567-024-01437-0","DOIUrl":"https://doi.org/10.1186/s13567-024-01437-0","url":null,"abstract":"<p><p>S. Typhimurium is a significant zoonotic pathogen, and its survival and transmission rely on stress resistance and virulence factors. Therefore, identifying key regulatory elements is crucial for preventing and controlling S. Typhimurium. We performed transcriptomic analysis and screened for a c-di-GMP pathway key gene STM0343, a putative EAL domain protein with an unknown function. Our findings revealed that the deletion of this gene (269ΔSTM0343) led to a 29.85% increase in c-di-GMP. In terms of stress resistance, the strain 269ΔSTM0343 showed significant improvements compared to the wild strain WT269. Specifically, it exhibited increases of 95.74% in extracellular protein and 35.96% in exopolysaccharide production by upregulating the expression of relevant genes. As a result, the biofilm formation ability of 269ΔSTM0343 was enhanced by 21.54%, accompanied by a more pronounced red, dry, and rough colony morphology. 269ΔSTM0343 also showed a 19.03% decrease in motility due to the downregulation of flhD expression. As a result, 269ΔSTM0343 increased resistance to various antibiotics, as well as to acidic conditions, oxidative stress, and disinfectants. In terms of virulence, compared to WT269, the adhesion and invasive ability of 269ΔSTM0343 to HeLa cells was enhanced by onefold and 25.67%, respectively. In in vivo experiments, mice challenged with 269ΔSTM0343 experienced greater weight loss, and the bacterial loads in the spleen, liver, and intestines were elevated by fivefold, 30-fold, and 21-fold, respectively, accompanied by more severe pathological damage. Mechanistic studies revealed that the adhesion and invasion capacities of 269ΔSTM0343ΔCsgB decreased by 29.41% and 68.58%, respectively, compared to 269ΔSTM0343. Additionally, LacZ gene reporting indicated that STM0343 inhibited the expression of CsgB. This suggests that STM0343 suppresses virulence by downregulating CsgB expression. This study provides insights into the regulatory mechanisms by which STM0343 reduces the stress resistance and pathogenicity of S. Typhimurium.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"13"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogen delivery route impacts disease severity in experimental Mycoplasma ovipneumoniae infection of domestic lambs.","authors":"Bryan Tegner Jacobson, Jessica DeWit-Dibbert, LaShae Zanca, Sobha Sonar, Carol Hardy, Michael Throolin, Patricia C Brewster, Kaitlyn Andujo, Kerri Jones, Jonathon Sago, Stephen Smith, Lizabeth Bowen, Diane Bimczok","doi":"10.1186/s13567-024-01439-y","DOIUrl":"10.1186/s13567-024-01439-y","url":null,"abstract":"<p><p>M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M. ovipneumoniae infection have reported highly variable clinical signs and pathology. Here, we assessed the impact of administering M. ovipneumoniae to the upper respiratory tract (URT) or to the lower respiratory tract (LRT) of two-month-old specific pathogen-free lambs. Lambs were inoculated with PBS (control) or with ceftiofur-treated nasal wash fluid obtained from sheep with natural M. ovipneumoniae infection, monitored for eight weeks, and subsequently euthanized. All lambs in the URT and LRT groups developed a stable infection with M. ovipneumoniae. M. ovipneumoniae infection led to lower weight gains and mild respiratory disease, with significantly greater effects following LRT inoculation compared to URT inoculation. At necropsy, lambs inoculated via the LRT showed consolidation of the cranial lung lobes. In addition, histological signs of  alveolar, bronchiolar, and interstitial inflammation were significantly more severe in the LRT compared to the URT group. M. ovipneumoniae loads in the trachea and bronchi also were significantly higher after LRT than URT inoculation. Interestingly, 9/10 inoculated lambs also tested positive for M. haemolytica in nasal swab but not in bronchial swab samples. In summary, our study suggests that bypassing protective mechanisms of the URT by delivering respiratory pathogens to the LRT leads to more severe respiratory disease and lung damage than delivery to the URT.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"10"},"PeriodicalIF":3.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scoring of swine lung images: a comparison between a computer vision system and human evaluators.","authors":"Robert Valeris-Chacin, Beatriz Garcia-Morante, Marina Sibila, Albert Canturri, Isaac Ballarà Rodriguez, Ignacio Bernal Orozco, Ramon Jordà Casadevall, Pedro Muñoz, Maria Pieters","doi":"10.1186/s13567-024-01432-5","DOIUrl":"10.1186/s13567-024-01432-5","url":null,"abstract":"<p><p>Cranioventral pulmonary consolidation (CVPC) is a common lesion observed in the lungs of slaughtered pigs, often associated with Mycoplasma (M.) hyopneumoniae infection. There is a need to implement simple, fast, and valid CVPC scoring methods. Therefore, this study aimed to compare CVPC scores provided by a computer vision system (CVS; AI DIAGNOS) from lung images obtained at slaughter, with scores assigned by human evaluators. In addition, intra- and inter-evaluator variability were assessed and compared to intra-CVS variability. A total of 1050 dorsal view images of swine lungs were analyzed. Total lung lesion score, lesion score per lung lobe, and percentage of affected lung area were employed as outcomes for the evaluation. The CVS showed moderate accuracy (62-71%) in discriminating between non-lesioned and lesioned lung lobes in all but the diaphragmatic lobes. A low multiclass classification accuracy at the lung lobe level (24-36%) was observed. A moderate to high inter-evaluator variability was noticed depending on the lung lobe, as shown by the intraclass correlation coefficient (ICC: 0.29-0.6). The intra-evaluator variability was low and similar among the different outcomes and lung lobes, although the observed ICC slightly differed among evaluators. In contrast, the CVS scoring was identical per lobe per image. The results of this study suggest that the CVS AI DIAGNOS could be used as an alternative to the manual scoring of CVPC during slaughter inspections due to its accuracy in binary classification and its perfect consistency in the scoring.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"9"},"PeriodicalIF":3.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9-editing of PRNP in Alpine goats.","authors":"Aurélie Allais-Bonnet, Christophe Richard, Marjolaine André, Valérie Gelin, Marie-Christine Deloche, Aurore Lamadon, Gwendoline Morin, Béatrice Mandon-Pépin, Eugénie Canon, Dominique Thépot, Johann Laubier, Katayoun Moazami-Goudarzi, Ludivine Laffont, Olivier Dubois, Thierry Fassier, Patrice Congar, Olivier Lasserre, Tiphaine Aguirre-Lavin, Jean-Luc Vilotte, Eric Pailhoux","doi":"10.1186/s13567-024-01444-1","DOIUrl":"10.1186/s13567-024-01444-1","url":null,"abstract":"<p><p>Misfolding of the cellular PrP (PrP^c) protein causes prion disease, leading to neurodegenerative disorders in numerous mammalian species, including goats. A lack of PrP^c induces complete resistance to prion disease. The aim of this work was to engineer Alpine goats carrying knockout (KO) alleles of PRNP, the PrP^c-encoding gene, using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the PRNP^Ter mutation previously described in Norwegian goats. Genome editors were injected under the zona pellucida prior to the electroporation of 565 Alpine goat embryos/oocytes. A total of 122 two-cell-stage embryos were transferred to 46 hormonally synchronized recipient goats. Six of the goats remained pregnant and naturally gave birth to 10 offspring. Among the 10 newborns, eight founder animals carrying PRNP genome-edited alleles were obtained. Eight different mutated alleles were observed, including five inducing KO mutations. Three founders carried only genome-edited alleles and were phenotypically indistinguishable from their wild-type counterparts. Among them, one male carrying a one base pair insertion leading to a KO allele is currently used to rapidly extend a PRNP-KO line of Alpine goats for future characterization. In addition to KO alleles, a PRNP^del6 genetic variant has been identified in one-third of founder animals. This new variant will be tested for its potential properties with respect to prion disease. Future studies will also evaluate the effects of genetic background on other characters associated with PRNP KO, as previously described in the Norwegian breed or other species.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"11"},"PeriodicalIF":3.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}