Revisiting the quantitative trait loci for milk production traits on BTA6

Weikard, Rosemarie; Widmann, Philipp; Buitkamp, Johannes; Emmerling, Reiner; Kühn, Christa

doi:10.1111/j.1365-2052.2011.02258.x

Cited by 24 publications

(22 citation statements)

References 19 publications

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“…PPARGC1A has been shown to play a pivotal role in the regulation of cellular energy metabolism, such as hepatic gluconeogenesis with response to fasting and food deprivation in other species (59,61), and to be a key gene in mitochondrial oxidative phosphorylation metabolism (43,51,58). In our previous studies, polymorphisms in the bovine PPARGC1A gene were found to be associated with milk performance traits in GH populations (73,74). In the present study, hepatic PPARGC1A mRNA abundance showed correlations to transcripts of genes included in the gluconeogenesis pathway and INSR, but not to MY.…”

Section: Resultsmentioning

confidence: 98%

Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows

Weikard

Goldammer

Brunner

et al. 2012

Physiological Genomics

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The molecular mechanisms regulating the physiological adaptation of tissues important for nutrient partitioning and metabolism in lactating cows are still not completely understood. The aim of our study was to identify tissue-specific regulatory mechanisms necessary to accommodate metabolic changes associated with different genetic potential for milk performance. For this purpose, we analyzed mRNA expression of genes involved in energy metabolism of segregating F(2) beef type cows with a combined genetic dairy and beef background (Charolais × German Holstein cross, CH×GH) in contrast to purebred German Holstein (GH) dairy cows. Three groups of cows differing in milk performance were examined using quantitative real-time PCR in liver, mammary gland, and skeletal muscle. Our results describe substantial tissue-specific differences in mRNA transcription profiles between cow groups in relation to their genetic potential for milk performance and highlight genes exhibiting specific, partially yet-unknown functions in dairy and beef type cows, e.g., upregulation of PCK2 transcripts in the mammary gland and FBP2 transcripts in skeletal muscle of dairy cows. Noticeably, PCCA and PPARGC1A mRNA abundance varied significantly across experimental groups in all three tissues, pointing to potential key gene functions in the metabolic adaptation relative to divergent milk production performance. Correlations of mRNA expression levels to milk performance traits indicate that gene transcriptional processes may play a regulatory role in liver, mammary gland, and skeletal muscle to enable cows with different genetic potential for milk performance to cope with metabolic lactation-associated challenges.

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Section: Resultsmentioning

confidence: 98%

Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows

Weikard

Goldammer

Brunner

et al. 2012

Physiological Genomics

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“…ABCG2 plays an important role in the transport of nutrients into milk, especially riboflavin (vitamin B 2 ) [36] and has been identified as the candidate gene underlying a quantitative trait locus on bovine chromosome 6 that affects milk yield and composition [37,38]. Therefore, the down-regulation of ABCG2 in quarters neighbouring E. coli infected quarters may be associated with the decrease in milk yield and casein synthesis, which was observed in these animals [10,39] and may imply a nutrient deficiency in milk from these animals.…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli- and Staphylococcus aureus-induced mastitis differentially modulate transcriptional responses in neighbouring uninfected bovine mammary gland quarters

et al. 2013

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BackgroundThe most important disease of dairy cattle is mastitis, caused by the infection of the mammary gland by various micro-organisms. Although the transcriptional response of bovine mammary gland cells to in vitro infection has been studied, the interplay and consequences of these responses in the in vivo environment of the mammary gland are less clear. Previously mammary gland quarters were considered to be unaffected by events occurring in neighbouring quarters. More recently infection of individual quarters with mastitis causing pathogens, especially Escherichia coli, has been shown to influence the physiology of neighbouring uninfected quarters. Therefore, the transcriptional responses of uninfected mammary gland quarters adjacent to quarters infected with two major mastitis causing pathogens, E. coli and Staphylococcus aureus, were compared.ResultsThe bacteriologically sterile, within-animal control quarters exhibited a transcriptional response to the infection of neighbouring quarters. The greatest response was associated with E. coli infection, while a weaker, yet significant, response occurred during S. aureus infection. The transcriptional responses of these uninfected quarters included the enhanced expression of many genes previously associated with mammary gland infections. Comparison of the transcriptional response of uninfected quarters to S. aureus and E. coli infection identified 187 differentially expressed genes, which were particularly associated with cellular responses, e.g. response to stress. The most affected network identified by Ingenuity Pathway analysis has the immunosuppressor transforming growth factor beta 1 (TGFB1) at its hub and largely consists of genes more highly expressed in control quarters from S. aureus infected cows.ConclusionsUninfected mammary gland quarters reacted to the infection of neighbouring quarters and the responses were dependent on pathogen type. Therefore, bovine udder quarters exhibit interdependence and should not be considered as separate functional entities. This suggests that mastitis pathogens not only interact directly with host mammary cells, but also influence discrete sites some distance away, which will affect their response to the subsequent spread of the infection. Understanding the underlying mechanisms may provide further clues for ways to control mammary gland infections. These results also have implications for the design of experimental studies investigating immune regulatory mechanisms in the bovine mammary gland.

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“…Y581S SNP is widely spread in some bovine breeds, reaching a frequency of 20% in the Israeli Holstein population (Ron et al, 2006), and it has been suggested as the causative polymorphism of a quantitative trait locus affecting the production of milk and its protein and fat composition (Cohen-Zinder et al, 2005;Weikard et al, 2012). In addition, a correlation has been suggested between this SNP and fertility (Komisarek and Dorynek, 2009).…”

Section: Introductionmentioning

confidence: 99%

The Bovine ATP-Binding Cassette Transporter ABCG2 Tyr581Ser Single-Nucleotide Polymorphism Increases Milk Secretion of the Fluoroquinolone Danofloxacin

et al. 2012

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The bovine adenosine triphosphate-binding cassette transporter G2 (ABCG2/breast cancer resistance protein) polymorphism Tyr581Ser (Y581S) has recently been shown to increase in vitro transepithelial transport of antibiotics. Since this transporter has been extensively related to the active secretion of drugs into milk, the potential in vivo effect of this polymorphism on secretion of xenobiotics in livestock could have striking consequences for milk production, the dairy industry, and public health. Our purpose was to study the in vivo effect of this polymorphism on the secretion of danofloxacin, a widely used veterinary antibiotic, into milk. Danofloxacin (1.25 mg/kg) was administered to six Y/Y 581 homozygous and six Y/S 581 heterozygous lactating cows, and plasma and milk samples were collected and analyzed by high-performance liquid chromatography. No differences were found in the pharmacokinetic parameters of danofloxacin in plasma between the two groups of animals. In contrast, Y/S heterozygous cows showed a 2-fold increase in danofloxacin levels in milk. In addition, the pharmacokinetic elimination parameters, mean residence time and elimination half-life, were significantly lower in the milk of the animals carrying the Y/S polymorphism. These in vivo results are in agreement with our previously published in vitro data, which showed a greater capacity of the S581 variant in accumulation assays, and demonstrate, for the first time, an important effect of the Y581S single-nucleotide polymorphism on antibiotic secretion into cow milk. These findings could be extended to other ABCG2 substrates, and may be relevant for the treatment of mastitis and for the design of accurate and novel strategies to handle milk residues. IntroductionThe ATP-binding cassette (ABC) transporter ABCG2 (breast cancer resistance protein) is expressed in a wide range of tissues and organs, including the intestine, liver, blood-brain barrier, and mammary gland (van Herwaarden and Schinkel, 2006). It affects the bioavailability of its substrates and mediates the active secretion of xenobiotics and several vitamins in milk (van Herwaarden et al., 2007). The occurrence of drug residues in milk could lead to the development of bacterial resistance, allergies, or hypersensitivity reactions in consumers (McManaman and Neville, 2003). On the other hand, effective treatments for mastitis may require a considerable transfer of drugs into milk (Escudero et al., 2007). All of these issues are of great concern for general public health, the dairy industry, and veterinary therapeutics. Hence, identification of relevant factors for the transfer of drugs into milk in livestock constitutes a priority.Changes in the expression and/or the function of ABCG2 can lead to dramatic variations in the pharmacokinetics and secretion of its substrates into milk Ni et al., 2010). Several single-nucleotide polymorphisms (SNPs) have been studied in human ABCG2, and of these, Gln141Lys (Q141K) is one of the most important, causing impaired urate transport wh...

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Revisiting the quantitative trait loci for milk production traits on BTA6

Cited by 24 publications

References 19 publications

Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows

Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows

Escherichia coli- and Staphylococcus aureus-induced mastitis differentially modulate transcriptional responses in neighbouring uninfected bovine mammary gland quarters

The Bovine ATP-Binding Cassette Transporter ABCG2 Tyr581Ser Single-Nucleotide Polymorphism Increases Milk Secretion of the Fluoroquinolone Danofloxacin

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