A natural knockout of the MYO7A gene leads to pre-weaning mortality in pigs.
Ontology highlight
ABSTRACT:
SUBMITTER: Derks MFL
PROVIDER: S-EPMC8360181 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
Publications
A natural knockout of the MYO7A gene leads to pre-weaning mortality in pigs.
Derks M F L MFL Megens H-J HJ Giacomini W L WL Groenen M A M MAM Lopes M S MS
Animal genetics 20210506 4
The pig breeding system provides a unique framework to study recessive defects and the consequence on the phenotype. We examined a commercial synthetic Duroc population for recessive defects and identified a haplotype on chromosome 9 significantly affecting pre-weaning mortality. To identify the causal variant underlying the mortality, we examined sequence data of four carrier animals and 21 non-carrier animals from the same population. The results yield a strong candidate causal stop-gained var ...[more]
Similar Datasets
Project description:Prebiotics, such as inulin, are non-digestible compounds that stimulate the growth of beneficial microbiota, which results in improved gut and overall health. In this study, we were interested to see if, and how, the ileal transcriptome altered after inulin administration in the pre-weaning period in pigs. Seventy-two Piétrain-Landrace newborn piglets were divided into three groups: (a) a control (CON) group (n = 24), (b) an inulin (IN)-0.5 group (n = 24), and (c) an IN-0.75 group (n = 24). Inulin was provided as a solution and administered twice a day. At week 4, eight piglets per group, those closest to the average in body weight, were sacrificed, and ileal scrapings were collected and analyzed using 3' mRNA massively parallel sequencing. Only minor differences were found, and three genes were differentially expressed between the CON and IN-0.5 group, at an FDR of 10%. All three genes were downregulated in the IN-0.5 group. When comparing the CON group with the IN-0.75 group, five genes were downregulated in the IN-0.75 group, including the three genes seen earlier as differentially expressed between CON and IN-0.5. No genes were found to be differential expressed between IN-0.5 and IN-0.75. Validation of a selection of these genes was done using qRT-PCR. Among the downregulated genes were Angiopoietin-like protein 4 (ANGPTL4), Aquaporin 7 (AQP7), and Apolipoprotein A1 (APOA1). Thus, although only a few genes were found to be differentially expressed, several of them were involved in lipid metabolism, belonging to the peroxisome proliferator-activated receptor (PPAR) signaling pathway and known to promote lipolysis. We, therefore, conclude that these lipid metabolism genes expressed in the ileum may play an important role when supplementing piglets with inulin early in life, before weaning.
| S-EPMC8539436 | biostudies-literature
Project description:To combat organ shortage in transplantation medicine, a novel strategy has been proposed to generate human organs from exogenous pluripotent stem cells utilizing the developmental mechanisms of pig embryos/foetuses. Genetically modified pigs missing specific organs are key elements in this strategy. In this study, we demonstrate the feasibility of using a genome-editing approach to generate anephrogenic foetuses in a genetically engineered pig model. SALL1 knockout (KO) was successfully induced by injecting genome-editing molecules into the cytoplasm of pig zygotes, which generated the anephrogenic phenotype. Extinguished SALL1 expression and marked dysgenesis of nephron structures were observed in the rudimentary kidney tissue of SALL1-KO foetuses. Biallelic KO mutations of the target gene induced nephrogenic defects; however, biallelic mutations involving small in-frame deletions did not induce the anephrogenic phenotype. Through production of F1 progeny from mutant founder pigs, we identified mutations that could reliably induce the anephrogenic phenotype and hence established a line of fertile SALL1-mutant pigs. Our study lays important technical groundwork for the realization of human kidney regeneration through the use of an empty developmental niche in pig foetuses.
| S-EPMC6541644 | biostudies-literature
Project description:IntroductionThe association between the porcine pre-weaning gut microbiota composition and diversity, and subsequent post-weaning diarrhea (PWD) susceptibility is currently being studied. In this longitudinal study, we examined the association between pre-weaning fecal microbiome composition and diversity, and PWD development in a Danish sow herd.MethodsForty-five pigs were followed from birth until 7 days after weaning (post-natal day (PND) 33). At PND 33, the pigs were categorized as PWD cases or healthy controls based on fecal consistency. We compared their fecal microbiomes at PND 8, late lactation (PND 27) and 7 days post weaning (PND 33) using 16S rRNA V3 region high-throughput sequencing. At PND 27 and 33, we also weighed the pigs, assessed fecal shedding of hemolytic Escherichia coli by culture and characterized hemolytic isolates by ETEC virulence factors with PCR and by whole genome sequencing.ResultsA total of 25 out of 45 pigs developed PWD and one Enterotoxigenic E. coli strain with F18:LT:EAST1 virotype was isolated from most pigs. At PND 33, we found differences in beta diversity between PWD and healthy pigs (R2 = 0.027, p = 0.009) and that body weight was associated with both alpha and beta diversity. Pre-weaning fecal microbiome diversity did not differ between PWD and healthy pigs and we found no significant, differentially abundant bacteria between them.ConclusionIn the production herd under study, pre-weaning fecal microbiome diversity and composition were not useful indicators of PWD susceptibility.
| S-EPMC10010570 | biostudies-literature
Project description:Weaning transition usually impairs intestinal architecture and functions and results in gut-associated disorders in pigs. Understanding the changes in intestinal transcriptome and gut microbiota during weaning transition is important for elucidating the underlying mechanism of weaning stress. In the present study, we performed RNA-seq to determine the changes in intestinal transcriptome and 16S rRNA sequencing to measure the gut microbiota changes in the weaning transition. Transcriptome results indicated that weaning transition altered intestinal gene expression involved in nutrient transport and metabolism. Regarding fatty metabolism, fatty acid-binding protein 1 (FABP1), acyl-CoA dehydrogenase (ACADSB), and carnitine palmitoyltransferase 2 (CPT2) expression in the intestine was decreased by weaning. Genes related to bile acid metabolism were increased by weaning, including FABP6, farnesoid X receptor (FXR or NR1H4) and organic solute transporter-α (SLC51A). In addition, genes associated with oxidative stress were altered by weaning transition, including decreased catalase (CAT) and lactate dehydrogenase (LDHA) and increased glutathione peroxidase 2 (GPX2) and superoxide dismutase 3 (SOD3). Results of microbiota composition showed that the Firmicutes abundance and Firmicutes/Bacteroidetes ratio were increased and that the Proteobacteria abundance in the fecal microbiota was decreased by the weaning process; during the weaning transition, the Bacteroides and Fusobacterium abundances decreased markedly, and these bacteria nearly disappeared, while the Prevotella abundance showed a marked increase. Moreover, the levels of the microbial metabolites butyrate and acetate increased with changes in gut microbiota composition. In addition, predictive metagenome by PICRUSt analysis showed that the pathways related to D-glutamine and D-glutamate metabolism, citrate cycle (TCA cycle), peroxisome proliferators-activated receptor (PPAR) signaling, alpha-linolenic acid metabolism were decreased and the pathway related to retinol metabolism was increased in the gut microbiota of piglets during weaning transition. Our results showed that early weaning alters intestinal gene expression involved in nutrient metabolism, which may be due to the changes in microbiota composition.
| S-EPMC7181064 | biostudies-literature
Project description:IntroductionA better understanding of the microbiota community in donkey foals during the weaning transition is a prerequisite to optimize gut function and improve feed efficiency. The objective of the present study was to investigate the dynamic changes in fecal microbiota in donkey foals from pre-to post-weaning period.MethodsA total of 27 fecal samples of donkey foals were collected in the rectum before morning feeding at pre-weaning (30 days of age, PreW group, n = 9), dur-weaning (100 days of age, DurW group, n = 9) and post-weaning (170 days of age, PostW group, n = 9) period. The 16S rRNA amplicon sequencing were employed to indicate the microbial changes during the weaning period.ResultsIn the present study, the cessation of breastfeeding gradually and weaning onto plant-based feeds increased the microbial diversity and richness, with a higher Shannon, Ace, Chao and Sobs index in DurW and PostW than in PreW (p < 0.05). The predominant bacterial phyla in donkey foal feces were Firmicutes (>50.5%) and Bacteroidota (>29.5%), and the predominant anaerobic fungi and archaea were Neocallimastigomycota and Euryarchaeota. The cellulolytic related bacteria including phylum Firmicutes, Spirochaetota and Fibrobacterota and genus norank_f_F082, Treponema, NK4A214_group, Lachnospiraceae_AC2044_group and Streptococcus were increased from pre-to post-weaning donkey foals (p < 0.05). Meanwhile, the functions related to the fatty acid biosynthesis, carbohydrate metabolism and amino acid biosynthesis were significantly enriched in the fecal microbiome in the DurW and PostW donkeys. Furthermore, the present study provided the first direct evidence that the initial colonization and establishment of anaerobic fungi and archaea in donkey foals began prior to weaning. The relative abundance of Orpinomyces were the highest in DurW donkey foals among the three groups (p < 0.01). In terms of archaea, the abundance of Methanobrevibacter were higher in PreW than in DurW and PostW (p < 0.01), but the abundance of Methanocorpusculum were significantly increased in DurW and PostW compared to PreW donkey foals (p < 0.01).DiscussionAltogether, the current study contributes to a comprehensive understanding of the development of the microbiota community in donkey foals from pre-to post-weaning period, which may eventually result in an improvement of the digestion and feed efficiency in donkeys.
| S-EPMC9915154 | biostudies-literature
Project description:Histone variant H3.3 is encoded by two genes, H3f3a and H3f3b, which can be expressed differentially depending on tissue type. Previous work in our lab has shown that knockout of H3f3b causes some neonatal lethality and infertility in mice, and chromosomal defects in mouse embryonic fibroblasts (MEFs). Studies of H3f3a and H3f3b null mice by others have produced generally similar phenotypes to what we found in our H3f3b nulls, but the relative impacts of the loss of either H3f3a or H3f3b have varied depending on the approach and genetic background. Here we used a knockout-first approach to target the H3f3a gene for inactivation in C57BL6 mice. Homozygous H3f3a targeting produced a lethal phenotype at or before birth. E13.5 null embryos had some potential morphological differences from WT littermates including smaller size and reduced head size. An E18.5 null embryo was smaller than its control littermates with several potential defects including small head and brain size as well as small lungs, which would be consistent with a late gestation lethal phenotype. Despite a reduction in H3.3 and total H3 protein levels, the only histone H3 post-translational modification in the small panel assessed that was significantly altered was the unique H3.3 mark phospho-Serine31, which was consistently increased in null neurospheres. H3f3a null neurospheres also exhibited consistent gene expression changes including in protocadherins. Overall, our findings are consistent with the model that there are differential, cell-type-specific contributions of H3f3a and H3f3b to H3.3 functions in epigenetic and developmental processes.
| S-EPMC10038898 | biostudies-literature
Project description:Piglet mortality is a complex phenotype that depends on the environment, selection on piglet health, but also on the interaction between the piglet and sow. However, also monogenic recessive defects contribute to piglet mortality. Selective breeding has decreased overall piglet mortality by improving both mothering abilities and piglet viability. However, variants underlying recessive monogenic defects are usually not well captured within the breeding values, potentially drifting to higher frequency as a result of intense selection or genetic drift. This study describes the identification by whole-genome sequencing of a recessive 16-bp deletion in the SPTBN4 gene causing postnatal mortality in a pig breeding line. The deletion induces a frameshift and a premature stop codon, producing an impaired and truncated spectrin beta non-erythrocytic 4 protein (SPTBN4). Applying medium density single nucleotide polymorphism (SNP) data available for all breeding animals, a pregnant carrier sow sired by a carrier boar was identified. Of the resulting piglets, two confirmed homozygous piglets suffered from severe myopathy, hind-limb paralysis, and tremors. Histopathological examination showed dispersed degeneration and decrease of cross-striations in the dorsal and hind-limb muscle fibers of the affected piglets. Hence, the affected piglets are unable to walk or drink, usually resulting in death within a few hours after birth. This study demonstrates how growing genomic resources in pig breeding can be applied to identify rare syndromes in breeding populations, that are usually poorly documented and often are not even known to have a genetic basis. The study allows to prevent carrier-by-carrier matings, thereby gradually decreasing the frequency of the detrimental allele and avoiding the birth of affected piglets, improving animal welfare. Finally, these "natural knockouts" increase our understanding of gene function within the mammalian clade, and provide a potential model for human disease.
| S-EPMC6902008 | biostudies-literature
Project description:High and variable pre-weaning mortality is a persistent problem in laboratory mouse breeding. Assuming a modest 15% mortality rate across mouse strains, means that approximately 1 million more pups are produced yearly in the EU to compensate for those which die. This paper presents the first large study under practical husbandry conditions to determine the risk factors associated with mouse pre-weaning mortality. We analysed historical records from 219,975 pups from two breeding facilities, collected as part of their management routine and including information on number of pups born and weaned per litter, parents' age and identification, and dates of birth and death of all animals. Pups were counted once in their first week of life and at weaning, and once every one or two weeks, depending on the need for cage cleaning. Dead pups were recorded as soon as these were found during the daily cage screening (without opening the cage). It was hypothesized that litter overlap (i.e. the presence of older siblings in the cage when new pups are born), a recurrent social configuration in trio-housed mice, is associated with increased newborn mortality, along with advanced dam age, large litter size, and a high number and age of older siblings in the cage. The estimated probability of pup death was two to seven percentage points higher in cages with litter overlap compared to those without. Litter overlap was associated with an increase in death of the entire litter of five and six percentage points, which represent an increase of 19% and 103% compared to non-overlapped litters in the two breeding facilities, respectively. Increased number and age of older siblings, advanced dam age, small litter size (less than four pups born) and large litter size (over 11 pups born) were associated with increased probability of pup death.
| S-EPMC7423063 | biostudies-literature
Project description:Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The role of MGL in tumorigenesis remains to be fully elucidated. We have previously shown that MGL expression was reduced or absent in multiple human malignancies, and overexpression of MGL inhibited cancer cell growth. Here, we have generated the MGL knockout mice to further investigate the role of MGL in tumorigenesis in vivo. Our results indicate that MGL-deficient (MGL+/-, MGL-/-) mice exhibited a higher incidence of neoplasia in multiple organs, including the lung, spleen, liver and lymphoid tissues. Interestingly, lung neoplasms were the most common neoplastic changes in the MGL-deficient mice. Importantly, MGL-deficient animals developed premalignant high-grade dysplasia and adenocarcinomas in their lungs. Investigation of the MGL expression status in lung cancer specimens from patients also revealed that MGL expression was significantly reduced in the majority of primary human lung cancers when compared to corresponding matched normal tissues. Furthermore, mouse embryonic fibroblasts (MEFs) from MGL-deficient animals showed characteristics of cellular transformation including increased cell proliferation, foci formation and anchorage-independent growth. Our results also indicate that MGL deficiency was associated with activation of EGFR and ERK. In addition, pro-inflammatory molecules COX-2 and TNF-α were also activated in the MGL-deficient lung tissues. Thus, our results provide new insights into the novel role of MGL as an important negative regulator of EGFR, COX-2 and TNF-α. Accordingly, EGFR and COX-2/TNF-α activation/induction is expected to play important roles in MGL deficiency-driven lung tumors. Collectively, our results implicate the tumor suppressive role of MGL in preventing tumor development in vivo, particularly in context to the lung cancer, and highlight its role as a potential tumor suppressor.
| S-EPMC5833374 | biostudies-literature
Project description:In pigs, the alpha-(1,2) fucosyltransferase (FUT1) gene has been highlighted for its properties in controlling the intestinal expression of enterotoxigenic E. coli (ETEC) F18 receptors; a pathogen causing edema disease and post-weaning diarrhoea. In this study, we hypothesized that pigs with different genotypes (ETEC F18 resistant (FUT1AA) versus susceptible (FUT1AG)) differed in following systemic and enteric responses: growth performance, plasma metabolic profiles, expression of candidate genes for intestinal mucosal homeostasis and immunity, number of selected bacteria and the concentration of short-chain fatty acids (SCFA) in faeces and digesta in piglets pre and post-weaning, and on the ETEC F18 adherence ex vivo. Genotype had the strongest impact on plasma metabolomic profile on day 7 and 28 of age. FUT1AG piglets had higher level of N-methyl-2-pyrrolidinone, hippuric acid, oxindole, and 3-oxo-5-beta-chol-7-en-24-oic acid on day 7, and a higher level of guanosine on day 28 than that in the FUT1AA piglets. FUT1AA piglets had a higher level of betaine on day 7 and 3-methylguanine on day 28. On day 34 of age, the FUT1AA pigs had higher levels of S-2-hydroxyglutarate, L-phenylalanine, tauroursodeoxycholic acid and an undetermined PC/LysoPC, while Ile Glu Phe Gly peptide and genistein 5-O-glucuronide, and PC (18:0/0:0) were at higher levels in the FUT1AG piglets. FUT1 genotype did not affect the growth performance and expression of candidate genes. FUT1AG piglets had a higher number of haemolytic bacteria in faeces and in digesta than that in FUT1AA at 34 days of age. The colonic acetic acid concentration was highest in FUT1AG piglets. FUT1 genotype may influence not only the expression of E. coli F18 receptors but could potentially impact the gut homeostasis and metabotype of piglets pre and post-weaning. Further investigations on the relation between FUT1 genotype and these aspects including the intestinal commensal microbiota will expand the knowledge on factors affecting the intestinal ecosystem.
| S-EPMC6110508 | biostudies-other