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Roomp, K., Kristinsson, H., Schvartz, D., Ubhayasekera, K., Sargsyan, E., Manukyan, L., . . . Bergsten, P. (2017). Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism. PLoS ONE, 12(4), Article ID e0176391.
Open this publication in new window or tab >>Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, e0176391Article in journal (Refereed) Published
Abstract [en]

Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucosestimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24: 1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our findings provide insight into how saturated fatty acids contribute to islet cell dysfunction by affecting the granule maturation process and confirmation in human islets of some previous findings from rodent islet and cell-line studies.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-323459 (URN)10.1371/journal.pone.0176391 (DOI)000400383600072 ()28448538 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme
Available from: 2017-06-07 Created: 2017-06-07 Last updated: 2017-11-29Bibliographically approved
Samgina, T. Y., Artemenko, K. A., Bergquist, J., Trebse, P., Torkar, G., Tolpina, M. D. & Lebedev, A. T. (2017). Differentiation of frogs from two populations belonging to the Pelophylax esculentus complex by LC-MS/MS comparison of their skin peptidomes. Analusis, 409(7), 1951-1961.
Open this publication in new window or tab >>Differentiation of frogs from two populations belonging to the Pelophylax esculentus complex by LC-MS/MS comparison of their skin peptidomes
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2017 (English)In: Analusis, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 7, 1951-1961 p.Article in journal (Refereed) Published
Abstract [en]

LC-MS/MS was applied to establish the composition of the skin peptidome of a Slovenian green frog belonging to the Pelophylax esculentus complex. As this was similar to the peptidome of the Moscow population of Pelophylax ridibundus, it allowed us to identify the Slovenian frog from the Pelophylax esculentus complex as Pelophylax ridibundus. The sequences of six new peptides from the brevinin 2 family are reported for the first time on the basis of manual interpretation of their tandem mass spectra. The structural similarity of the brevinin 2 peptides from the Moscow and Slovenian populations of Pelophylax ridibundus enables peptides from this family to be utilized as biomarkers for Pelophylax ridibundus inter- and intraspecies differentiation, and the proposed approach can be used as an analytical tool for differentiating the corresponding species and populations. The potential biological activities of the novel peptides were estimated by 2D mass mapping. The results allowed us to classify all of the available peptides belonging to the brevinin 2 family.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2017
Keyword
Natural products, Frog peptides, Brevinins, Green frogs, Tandem mass spectrometry, Peptide sequencing
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-319540 (URN)10.1007/s00216-016-0143-3 (DOI)000394377200023 ()28012108 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2017-11-29Bibliographically approved
Fallahsharoudi, A., de Kock, N., Johnsson, M., Bektic, L., Ubhayasekera, S. J., Bergquist, J., . . . Jensen, P. (2017). Genetic and Targeted eQTL Mapping Reveals Strong Candidate Genes Modulating the Stress Response During Chicken Domestication. G3: Genes, Genomes, Genetics, 7(2), 497-504.
Open this publication in new window or tab >>Genetic and Targeted eQTL Mapping Reveals Strong Candidate Genes Modulating the Stress Response During Chicken Domestication
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2017 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 7, no 2, 497-504 p.Article in journal (Refereed) Published
Abstract [en]

The stress response has been largely modified in all domesticated animals, offering a strong tool for genetic mapping. In chickens, ancestral Red Junglefowl react stronger both in terms of physiology and behavior to a brief restraint stress than domesticated White Leghorn, demonstrating modified functions of the hypothalamic-pituitary-adrenal (HPA) axis. We mapped quantitative trait loci (QTL) underlying variations in stress-induced hormone levels using 232 birds from the 12th generation of an advanced intercross between White Leghorn and Red Junglefowl, genotyped for 739 genetic markers. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), and pregnenolone (PREG) were measured using LC-MS/MS in all genotyped birds. Transcription levels of the candidate genes were measured in the adrenal glands or hypothalamus of 88 out of the 232 birds used for hormone assessment. Genes were targeted for expression analysis when they were located in a hormone QTL region and were differentially expressed in the pure breed birds. One genome-wide significant QTL on chromosome 5 and two suggestive QTL together explained 20% of the variance in corticosterone response. Two significant QTL for aldosterone on chromosome 2 and 5 (explaining 19% of the variance), and one QTL for DHEA on chromosome 4 (explaining 5% of the variance), were detected. Orthologous DNA regions to the significant corticosterone QTL have been previously associated with the physiological stress response in other species but, to our knowledge, the underlying gene(s) have not been identified. SERPINA10 had an expression QTL (eQTL) colocalized with the corticosterone QTL on chromosome 5 and PDE1C had an eQTL colocalized with the aldosterone QTL on chromosome 2. Furthermore, in both cases, the expression levels of the genes were correlated with the plasma levels of the hormones. Hence, both these genes are strong putative candidates for the domestication-induced modifications of the stress response in chickens. Improved understanding of the genes associated with HPA-axis reactivity can provide insights into the pathways and mechanisms causing stress-related pathologies.

Place, publisher, year, edition, pages
GENETICS SOCIETY AMERICA, 2017
Keyword
animal domestication, quantitative trait genes, corticosterone, aldosterone
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-319644 (URN)10.1534/g3.116.037721 (DOI)000394357100015 ()27974436 (PubMedID)
Funder
Swedish Research Council, 621-2011-4731 621-2011-4423, 2015-4870EU, European Research Council, 322206
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-11-29Bibliographically approved
Ljungvall, K., Magnusson, U., Korvela, M., Norrby, M., Bergquist, J. & Persson, S. (2017). Heavy metal concentrations in female wild mink (Neovison vison) in Sweden: Sources of variation and associations with internal organ weights. Environmental Toxicology and Chemistry, 36(8), 2030-2035.
Open this publication in new window or tab >>Heavy metal concentrations in female wild mink (Neovison vison) in Sweden: Sources of variation and associations with internal organ weights
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2017 (English)In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 36, no 8, 2030-2035 p.Article in journal (Refereed) Published
Abstract [en]

The American mink is an invasive species in Sweden, and it is legally hunted all year. Therefore, the mink is well suited as a sentinel species for environmental monitoring. In the present study female mink (n = 91) from 6 different areas in Sweden were analyzed for the concentrations of silver, cadmium, mercury and lead in liver tissue using inductively coupled plasma mass spectrometry. The wet concentrations in liver tissue were 42.6 +/- 52.7 ng/g for silver, 99.5 +/- 100 ng/g for cadmium, 652 +/- 537 ng/g formercury, and 196 +/- 401 ng/g for lead (expressed as mean + standard deviation). There were associations between the sample area and the concentrations of silver, lead, and mercury. The concentrations of lead and cadmium varied with season of capture and lead, cadmium, and mercury were positively associated with increasing age. Relative liver weight was positively associated with concentrations of mercury and negatively associated with lead and cadmium. Relative kidney weight was negatively associated with lead concentrations. In summary, it is of importance to take age and season of capture into account when assessing levels of heavy metals in wild mink. Also, liver and kidneys seem to be potential targets for heavy metal toxicity in wild female mink in Sweden.

Keyword
Wildlife toxicology, Metal accumulation, Metal toxicity, Mink, Liver, Kidney
National Category
Environmental Sciences Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-333514 (URN)10.1002/etc.3717 (DOI)000406398400011 ()
Available from: 2017-11-20 Created: 2017-11-20 Last updated: 2018-01-13Bibliographically approved
Edvinsson, Å., Bränn, E., Hellgren, C., Freyhult, E., White, R., Kamali-Moghaddam, M., . . . Sundström Poromaa, I. (2017). Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction. Psychoneuroendocrinology, 80, 15-25.
Open this publication in new window or tab >>Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
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2017 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, 15-25 p.Article in journal (Refereed) Published
Abstract [en]

Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.

Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.

Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.

Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2017
Keyword
Antenatal depression, Pregnancy, Inflammatory markers, Proximity extension assay, Selective serotonin reuptake inhibitors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-326211 (URN)10.1016/j.psyneuen.2017.02.027 (DOI)000402352200003 ()28292683 (PubMedID)
Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-08Bibliographically approved
Valdes, A., Garcia-Canas, V., Artemenko, K. A., Simo, C., Bergquist, J. & Cifuentes, A. (2017). Nano-liquid Chromatography-orbitrap MS-based Quantitative Proteomics Reveals Differences Between the Mechanisms of Action of Carnosic Acid and Carnosol in Colon Cancer Cells. Molecular & cellular proteomics (online), 16(1), 8-22.
Open this publication in new window or tab >>Nano-liquid Chromatography-orbitrap MS-based Quantitative Proteomics Reveals Differences Between the Mechanisms of Action of Carnosic Acid and Carnosol in Colon Cancer Cells
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2017 (English)In: Molecular & cellular proteomics (online), ISSN 1535-9476, E-ISSN 1535-9484, Vol. 16, no 1, 8-22 p.Article in journal (Refereed) Published
Abstract [en]

Carnosic acid (CA) and carnosol (CS) are two structurally related diterpenes present in rosemary herb (Rosmarinus officinalis). Although several studies have demonstrated that both diterpenes can scavenge free radicals and interfere in cellular processes such as cell proliferation, they may not necessarily exert the same effects at the molecular level. In this work, a shotgun proteomics study based on stable isotope dimethyl labeling (DML) and nano -liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) has been performed to identify the relative changes in proteins and to gain some light on the specific molecular targets and mechanisms of action of CA and CS in HT-29 colon cancer cells. Protein profiles revealed that CA and CS induce different Nrf2-mediated response. Furthermore, examination of our data revealed that each diterpene affects protein homeostasis by different mechanisms. CA treatment induces the expression of proteins involved in the unfolded protein response in a concentration dependent manner reflecting ER stress, whereas CS directly inhibits chymotrypsin-like activity of the 20S proteasome. In conclusion, the unbiased proteomics-wide method applied in the present study has demonstrated to be a powerful tool to reveal differences on the mechanisms of action of two related bioactive compounds in the same biological model.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-316126 (URN)10.1074/mcp.M116.061481 (DOI)000392205300002 ()27834734 (PubMedID)
Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2017-11-29Bibliographically approved
Sui, P., Watanabe, H., Artemenko, K., Sun, W., Bakalkin, G., Andersson, M. & Bergquist, J. (2017). Neuropeptide imaging in rat spinal cord with MALDI-TOF MS: Method development for the application in pain-related disease studies. European journal of mass spectrometry, 23(3), 105-115.
Open this publication in new window or tab >>Neuropeptide imaging in rat spinal cord with MALDI-TOF MS: Method development for the application in pain-related disease studies
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2017 (English)In: European journal of mass spectrometry, ISSN 1469-0667, E-ISSN 1751-6838, Vol. 23, no 3, 105-115 p.Article in journal (Refereed) Published
Abstract [en]

Spinal cord as a connection between brain and peripheral nervous system is an essential material for studying neural transmission, especially in pain-related research. This study was the first to investigate pain-related neuropeptide distribution in rat spinal cord using a matrix-assisted laser desorption ionization-time of flight imaging mass spectrometry (MALDI TOF MS) approach. The imaging workflow was evaluated and showed that MALDI TOF MS provides efficient resolution and robustness for neuropeptide imaging in rat spinal cord tissue. The imaging result showed that in naive rat spinal cord the molecular distribution of haeme, phosphatidylcholine, substance P and thymosin beta 4 were well in line with histological features. Three groups of pain-related neuropeptides, which are cleaved from prodynorphin, proenkephalin and protachykinin-1 proteins were detected. All these neuropeptides were found predominantly localized in the dorsal spinal cord and each group had unique distribution pattern. This study set the stage for future MALDI TOF MS application to elucidate signalling mechanism of pain-related diseases in small animal models.

Keyword
Matrix-assisted laser desorption ionization-time of flight imaging mass spectrometry, neuropathic pain, neuropeptide imaging, rat spinal cord
National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-330364 (URN)10.1177/1469066717703272 (DOI)000405717700004 ()28657437 (PubMedID)
Funder
Swedish Research Council, 621-2011-4423, 2015-4870
Available from: 2017-09-28 Created: 2017-09-28 Last updated: 2018-01-13Bibliographically approved
Warnecke, A., Musunuri, S., N'diaye, M., Sandalova, T., Achour, A., Bergquist, J. & Harris, R. A. (2017). Nitration of MOG diminishes its encephalitogenicity depending on MHC haplotype. Journal of Neuroimmunology, 303, 1-12.
Open this publication in new window or tab >>Nitration of MOG diminishes its encephalitogenicity depending on MHC haplotype
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2017 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 303, 1-12 p.Article in journal (Refereed) Published
Abstract [en]

Post-translational modifications of autoantigens are hypothesized to affect their immunogenicity. We here report that nitration of tyrosine 40 in Myelin Oligodendrocyte Glycoprotein (MOG) abrogates its encephalitogenicity both at protein and peptide levels in the experimental autoimmune encephalomyelitis (EAE) model in H2(b) C57BL/6 mice. Furthermore, nitrated MOG displays inferior antigen-specific proliferation of 2D2 splenocytes in vitro. Conversely, H2(q) DBA1 mice remain fully susceptible to EAE induction using nitrated MOG as the dominant epitope of H2q mice is unaltered. Molecular modeling analysis of the MOG(35-55)/H2-lA(b) complex and bioinformatics peptide binding predictions indicate that the lack of T cell reactivity towards nitrated MOG can be attributed to the inability of murine H2-IA(b) to efficiently present the altered peptide ligand of MOG(35-55) because the nitrated tyrosine 40 cannot be accommodated in the p1 anchor pocket. In conclusion we demonstrate nitration as a relevant determinant affecting T cell recognition of carrier antigen depending on MHC haplotype. Our data have implications for understanding the role of post-translationally modified antigen in autoimmunity. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.

Keyword
3-Nitrotyrosine, Post-translational modification, Myelin oligodendrocyte glycoprotein, Experimental autoimmune encephalomyelitis, Antigen presentation, Major histocompatibility complex, Autoimmunity, Oxidative stress, Epitope spreading
National Category
Neurosciences Immunology
Identifiers
urn:nbn:se:uu:diva-317945 (URN)10.1016/j.jneuroim.2016.11.008 (DOI)000393629100001 ()28011088 (PubMedID)
Available from: 2017-04-01 Created: 2017-04-01 Last updated: 2018-01-13Bibliographically approved
Staaf, J., Labmayr, V., Paulmichl, K., Manell, H., Cen, J., Ciba, I., . . . Kullberg, J. (2017). Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity. Pancreas, 46(3), 358-365.
Open this publication in new window or tab >>Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity
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2017 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, 358-365 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further.

METHODS: We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging.

RESULTS: The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS.

CONCLUSIONS: In adolescents with obesity, PFF is elevated and associatedto MetS, fasting glucose, and visceral adipose tissue but not to beta-cellfunction, glucose tolerance, or BMI-SDS. This study demonstrates thatconclusions regarding PFF and its associations depend on the body massfeatures of the cohort.

Keyword
pancreatic fat, pediatric obesity, beta-cell function, metabolic syndrome, body mass index-standard deviation score
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-311308 (URN)10.1097/MPA.0000000000000771 (DOI)000394448600018 ()27941426 (PubMedID)
Funder
Swedish Research Council, 72X-14019 2012-2330 2011-4423Swedish Diabetes AssociationEU, FP7, Seventh Framework Programme, 279153
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2017-04-26Bibliographically approved
Fallahsharoudi, A., de Kock, N., Johnsson, M., Bektic, L., Ubhayasekera, S. J., Bergquist, J., . . . Jensen, P. (2017). QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl. Molecular and Cellular Endocrinology, 446(C), 52-58.
Open this publication in new window or tab >>QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl
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2017 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 446, no C, 52-58 p.Article in journal (Refereed) Published
Abstract [en]

Domestication of animals is associated with numerous alterations in physiology, morphology, and behavior. Lower reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and reduced fearfulness is seen in most studied domesticates, including chickens. Previously we have shown that the physiological stress response as well as expression levels of hundreds of genes in the hypothalamus and adrenal glands are different between domesticated White Leghorn and the progenitor of modern chickens, the Red Junglefowl. To map genetic loci associated with the transcription levels of genes involved in the physiological stress response, we conducted an eQTL analysis in the F12 generation of an inter-cross between White Leghorn and Red Junglefowl. We selected genes for further studies based on their known function in the regulation of the HPA axis or sympathoadrenal (SA) system, and measured their expression levels in the hypothalamus and the adrenal glands after a brief stress exposure (physical restraint). The expression values were treated as quantitative traits for the eQTL mapping. The plasma levels of corticosterone were also assessed. We analyzed the correlation between gene expression and corticosterone levels and mapped eQTL and their potential effects on corticosterone levels. The effects on gene transcription of a previously found QTL for corticosterone response were also investigated. The expression levels of the glucocorticoid receptor (GR) in the hypothalamus and several genes in the adrenal glands were correlated with the post-stress levels of corticosterone in plasma. We found several cis- and transacting eQTL for stress-related genes in both hypothalamus and adrenal. In the hypothalamus, one eQTL for c-FOS and one QTL for expression of GR were found. In the adrenal tissue, we identified eQTL for the genes NROB1, RGS4, DBH, MAOA, GRIN1, GABRB2, GABRB3, and HSF1. None of the found eQTL were significant predictors of corticosterone levels. The previously found QTL for corticosterone was associated with GR expression in hypothalamus. Our data suggests that domestication related modification in the stress response is driven by changes in the transcription levels of several modulators of the HPA and SA systems in hypothalamus and adrenal glands and not by changes in the expression of the steroidogenic genes. The presence of eQTL for GR in hypothalamus combined with the negative correlation between GR expression and corticosterone response suggests GR as a candidate for further functional studies regarding modification of stress response during chicken domestication.

Keyword
Animal domestication, Stress response, HPA axis, QTL, eQTL
National Category
Medical Genetics Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-322082 (URN)10.1016/j.mce.2017.02.010 (DOI)000399509600006 ()
Funder
Swedish Research Council, 621-2011-4731Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 221-2011-1088EU, European Research Council, Genewell 322206
Available from: 2017-05-18 Created: 2017-05-18 Last updated: 2018-01-13Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4597-041x

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