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Background: MG132, a proteasome inhibitor, is widely used to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity by proteasome-mediated degradation of IκB. It has been marketed as a specific, reversible, cell-permeable and low-cost inhibitor. However, adverse effects of the compound have been reported in the literature. We recently discovered and characterised a point mutation in the acute phase protein serum amyloid A (SAA) in chickens, by overexpressing the protein in chicken hepatocellular carcinoma (LMH) cells. This serine to arginine exchange at amino acid position 90 (SAA.R90S) leads to intra- and extracellular accumulation of SAA, which is surprisingly counteracted by MG132 treatment, independent of SAA's intrinsic promoter., Methods and Results: To test, whether low proteasomal degradation of SAA.R90S is responsible for the observed intra- and extracellular SAA accumulation, we intended to inhibit the proteasome in SAA wild type (SAA.WT) overexpressing cells with MG132. However, we observed an unexpected drastic decrease in SAA protein expression at the transcript level. NF-κB gene expression was unchanged by MG132 at the measured time point., Conclusions: The observed results demonstrate that MG132 inhibits SAA expression at the transcript level, independent of its endogenous promoter. Further, the data might indicate that NF-κB is not involved in the observed MG132-induced inhibition of SAA expression. We, consequently, question in this brief report whether MG132 should truly be categorised as a specific ubiquitin proteasome inhibitor and recommend the usage of alternative compounds., (© 2024. The Author(s).)

The poultry meat production landscape has undergone a reduction in chicken breeds, resulting in a reliance on a limited number of varieties. Motivated by the goal of promoting sustainable chicken production and enhancing agro-biodiversity, this study pioneers a comparison between local chicken breeds (LB) and their crossbreeds (CB) with modern hybrid lines. Serving as an initial exploration within a larger project, this research acts as a prelude to a comprehensive investigation, aiming to complement the human sensory assessment of product quality. Study I assessed chicken broths prepared from 3 German LBs Bielefelder (BIE), Altsteirer (ALT), and Ramelsloher (RAM) utilizing a factorial 3 × 2 × 2 design that incorporated variations in salt content (unsalted/salted) and cooking time (1 h/3 h). The sensory profiles of the LB broths were largely similar, except for BIE, which exhibited a higher skin odor intensity. Both, increased salt content and longer cooking time intensify sensory perception on most attributes. In study II, BIE was compared with 6 CBs, with variations in salt content and cooking time (6 × 2 × 2 + 1 × 2 factorial design). BIE demonstrated higher sensory intensities than the CBs. Those were comparable, with no clear advantages or disadvantages identified from a sensory standpoint. These findings support that crossbreeding with commercial lines is not associated with changes in the sensory profile. It thus represents a strategy for improving the economic viability of local chicken breeds in order to preserve their valuable agro-biodiversity. The provided protocol for evaluating chicken broth from LBs or their CBs aims to offer researchers a standardized foundation for sensory assessments in chicken broth studies., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In spite of being controversial and raising ethical concerns, the application of gene editing is more likely to be accepted when it contributes to improving animal welfare. One of the animal welfare and ethical issues in chicken breeding is chick culling, the killing of the male layer chicks after hatching due to the poor fattening performance. Although establishing dual-purpose chicken lines could solve this problem, unfavorable genetic correlations between egg and meat production traits hindered their competitiveness. Although it is also controversial in ethical terms, gene editing may accelerate genetic progress in dual-purpose chicken and alleviate the ethical concerns from chick culling., Results: The simulation compared the utility improvement in dual-purpose use under two breeding schemes: one consisting in the improvement of the laying hens, and the second in the improvement of a synthetic line obtained from a layer broiler cross. In each breeding scheme, the breeding programs were simulated with and without gene editing. Polygenic breeding values and 500 simulated quantitative trait loci (QTL) with different levels of pleiotropy caused negative correlations between egg production, meat production, and overall health. The results of the simulation demonstrated that genetic gain could be accelerated by at most 81% for several generations if gene editing was used. The actual increase in genetic gain depended on the number of single nucleotide polymorphisms (SNPs) being edited per animal. The rate of genetic improvement became equal in scenarios with and without gene editing after 20 generations. This is because the remaining segregating QTL had small effects and their edition would have negative overall health effects from potential off-target edits. Although gene editing can improve genetic gain in quantitative traits, it can only be recommended as long as QTL with reasonable effect sizes are segregating and detectable., Conclusions: This simulation demonstrates the potential of gene editing to accelerate the simultaneous improvement of negatively correlated traits. When the risk of negative consequences from gene editing persists, the number of SNPs to be edited should be chosen carefully to obtain the optimal genetic gain., (© 2024. The Author(s).)

Feather pecking (FP) is a damaging nonaggressive behavior in laying hens with a heritable component. Its occurrence has been linked to the immune system, the circadian clock, and foraging behavior. Furthermore, dysregulation of miRNA biogenesis, disturbance of the gamma-aminobutyric acid (GABAergic) system, as well as neurodevelopmental deficiencies are currently under debate as factors influencing the propensity for FP behavior. Past studies, which focused on the dissection of the genetic factors involved in FP, relied on single nucleotide polymorphisms (SNPs) and short insertions and deletions < 50 bp (InDels). These variant classes only represent a certain fraction of the genetic variation of an organism. Hence, we reanalyzed whole-genome sequencing data from two experimental populations, which have been divergently selected for FP behavior for over more than 15 generations, performed variant calling for structural variants (SVs) as well as tandem repeats (TRs), and jointly analyzed the data with SNPs and InDels. Genotype imputation and subsequent genome-wide association studies, in combination with expression quantitative trait loci analysis, led to the discovery of multiple variants influencing the GABAergic system. These include a significantly associated TR downstream of the GABA receptor subunit beta-3 (GABRB3) gene, two microRNAs targeting several GABA receptor genes, and dystrophin (DMD), a direct regulator of GABA receptor clustering. Furthermore, we found the transcription factor ETV1 to be associated with the differential expression of 23 genes, which points toward a role of ETV1, together with SMAD4 and KLF14, in the disturbed neurodevelopment of high-feather pecking chickens., (© 2022. The Author(s).)

Background: Feather pecking (FP) is damaging behavior in laying hens leading to global economic losses in the layer industry and massive impairments of animal welfare. The objective of the study was to discover genetic variants and affected genes that lead to FP behavior. To achieve that we imputed low-density genotypes from two different populations of layers divergently selected for FP to sequence level by performing whole genome sequencing on founder and half-sib individuals. In order to decipher the genetic structure of FP, genome wide association studies and meta-analyses of two resource populations were carried out by focusing on the traits 'feather pecks delivered' (FPD) and the 'posterior probability of a hen to belong to the extreme feather pecking subgroup' (pEFP)., Results: In this meta-analysis, we discovered numerous genes that are affected by polymorphisms significantly associated with the trait FPD. Among them SPATS2L, ZEB2, KCHN8, and MRPL13 which have been previously connected to psychiatric disorders with the latter two being responsive to nicotine treatment. Gene set enrichment analysis revealed that phosphatidylinositol signaling is affected by genes identified in the GWAS and that the Golgi apparatus as well as brain structure may be involved in the development of a FP phenotype. Further, we were able to validate a previously discovered QTL for the trait pEFP on GGA1, which contains variants affecting NIPA1, KIAA1211L, AFF3, and TSGA10., Conclusions: We provide evidence for the involvement of numerous genes in the propensity to exhibit FP behavior that could aid in the selection against this unwanted trait. Furthermore, we identified variants that are involved in phosphatidylinositol signaling, Golgi metabolism and cell structure and therefore propose changes in brain structure to be an influential factor in FP, as already described in human neuropsychiatric disorders.

Background: Feather pecking (FP) in laying hens reduces animal welfare and leads to economic losses for the layer industry. FP is considered a heritable condition that is influenced by dysregulation of neurotransmitter homeostasis, the gut microbiome, and the immune system. To identify genes and biological pathways responsible for FP behavior we compared the brain transcriptomes of 48 hens divergently selected for FP. In addition, we tested if high feather peckers (HFP) and low feather peckers (LFP) respond differently to light since light has been shown to trigger FP behavior., Results: Of approximately 48 million reads/sample an average of 98.4% were mapped to the chicken genome (GRCg6a). We found 13,070 expressed genes in the analyzed brains of which 423 showed differential expression between HFP and LFP. Genes of uncertain function and non-coding RNAs were overrepresented among those transcripts. Functional analyses revealed the involvement of cholinergic signaling, postsynaptic activity, membrane channels, and the immune system. After the light stimulus, 28 genes were found to be differentially expressed. These included an interaction cluster of core components of the circadian clock. However, differences in the response to light between HFP and LFP were not detectable., Conclusions: Genes involved in cholinergic signaling, channel activity, synaptic transmission, and immune response were found to be involved in FP behavior. We propose a model in which the gut microbiota modulates the immune system, which in turn affects cholinergic signaling. This might have an influence on monoamine signaling with possible involvement of GABA or glutamate signaling.

Background: Feather pecking and aggressive pecking in laying hens are serious economic and welfare issues. In spite of extensive research on feather pecking during the last decades, the motivation for this behavior is still not clear. A small to moderate heritability has frequently been reported for these traits. Recently, we identified several single-nucleotide polymorphisms (SNPs) associated with feather pecking by mapping selection signatures in two divergent feather pecking lines. Here, we performed a genome-wide association analysis (GWAS) for feather pecking and aggressive pecking behavior, then combined the results with those from the recent selection signature experiment, and linked them to those obtained from a differential gene expression study., Methods: A large F2 cross of 960 F2 hens was generated using the divergent lines as founders. Hens were phenotyped for feather pecks delivered (FPD), aggressive pecks delivered (APD), and aggressive pecks received (APR). Individuals were genotyped with the Illumina 60K chicken Infinium iSelect chip. After data filtering, 29,376 SNPs remained for analyses. Single-marker GWAS was performed using a Poisson model. The results were combined with those from the selection signature experiment using Fisher's combined probability test., Results: Numerous significant SNPs were identified for all traits but with low false discovery rates. Nearly all significant SNPs were located in clusters that spanned a maximum of 3 Mb and included at least two significant SNPs. For FPD, four clusters were identified, which increased to 13 based on the meta-analysis (FPD meta ). Seven clusters were identified for APD and three for APR. Eight genes (of the 750 investigated genes located in the FPD meta clusters) were significantly differentially-expressed in the brain of hens from both lines. One gene, SLC12A9, and the positional candidate gene for APD, GNG2, may be linked to the monomanine signaling pathway, which is involved in feather pecking and aggressive behavior., Conclusions: Combining the results from the GWAS with those of the selection signature experiment substantially increased the statistical power. The behavioral traits were controlled by many genes with small effects and no single SNP had effects large enough to justify its use in marker-assisted selection.

Feather pecking is a serious problem to the layer industry severely impairing animal welfare and causing economic losses. As a measure to control this unwanted behavior, beak trimming has been applied in the past, but is now banned in more and more countries including Germany. The propensity to perform feather pecking is a heritable trait. It can be reduced by means of breeding, but it is a hard-to-measure trait and to establish suitable selection schemes, knowledge of the genetic architecture of the trait is needed. Commercial flocks are of limited use for this research purpose for several reasons, but selection lines offer the possibility to realize advanced experimental designs. Here, a selective review on fundamental-type research is presented that has been conducted in the Hohenheim selection lines over the past years. Based thereon and the available literature, a mechanistic hypothesis about feather pecking is developed and it gives a perspective on implications for practical breeding. [ABSTRACT FROM AUTHOR]