Production of bovine alpha-lactalbumin in the milk of transgenic pigs.

Bleck, Gregory T.; White, Brett R.; Miller, David J.; Wheeler, M. B.

doi:10.2527/1998.76123072x

Cited by 79 publications

(45 citation statements)

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“…α-LA is a small, acidic, molten-globule, cation-binding milk protein, which has several important biological functions, such as lactose synthesis and Ca 2+ binding (Lonnerdal and Glazier, 1985;Bleck et al, 1998). In addition, α-LA has been linked to antimicrobial activity (Pellegrini et al, 1999;Kilara and Panyam, 2003), reduction of stress (Markus et al, 2000), immunomodulation (Brody, 2000;Cross and Gill, 2000), regulation of cell growth (Sternhagen and Allen, 2001), antiulcer activity (Matsumoto et al, 2001), and antihypertensive activity (Fitzgerald et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Association between a polymorphism of the α-lactalbumin gene and milk production traits in Chinese Holstein cows

Zhang¹,

Dong²

2013

Genet. Mol. Res.

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ABSTRACT. The traits particularly important for milk production include milk yield, protein percentage, fat percentage, and the somatic cell score. Alpha-lactalbumin (α-LA) is an important whey protein of cow milk, and is also present in the milk of many other mammalian species. In this study, we analyzed the genetic polymorphisms of the α-LA gene and their relationship to milk production traits (milk yield, protein percentage, fat percentage, and somatic cell score) in Chinese Holstein cows. The goal of this study was to contribute further molecular genetic information related to dairy cattle, to determine the molecular markers that are most closely linked with milk production traits, and to provide a scientific basis for the improvement of economically relevant traits in cows. Fluorescence-based conformation-sensitive gel electrophoresis, DNA sequencing, and ligation detection reaction techniques were used to analyze genetic variations of the α-LA gene (5ꞌ-UTR, exons 1, 2, 3, 4, and 3ꞌ-UTR) in 923 Chinese Holstein cows. One novel single nucleotide polymorphism (SNP), α-LA2516, was identified in exon 4 of the α-LA gene. Allele frequencies were as follows: T 0.674, C 0.326. Association analysis revealed that α-LA2516 was not associated with milk yield, These findings suggest that the SNP α-LA2516 in the α-LA gene likely does not have potential as a molecular marker for milk production traits in Chinese Holstein cows.

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Section: Introductionmentioning

confidence: 99%

Association between a polymorphism of the α-lactalbumin gene and milk production traits in Chinese Holstein cows

Zhang¹,

Dong²

2013

Genet. Mol. Res.

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“…Similar tools may also be used to improve animal production, including the modification of milk composition for human and animal consumption (Bleck et al, 1998;Hiripi et al, 2000;Brophy et al, 2003;Houdebine, 2004;Soler et al, 2006;Baranyi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Rabbit milk protein genes: from mRNA identification to chromatin structure

Jolivet

Daniel-Carlier

Thépot

et al. 2008

Animal

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Milk protein genes are among the most intensively expressed and they are active only in epithelial mammary cells of lactating animals. They code for proteins which represent 30% of the proteins consumed by humans in developed countries. Mammary gland development occurs essentially during each pregnancy. This offers experimenters attractive models to study the expression mechanisms of genes controlled by known hormones and factors (prolactin, glucocorticoids, progesterone, insulin-like growth factor-1 and others) as well as extracellular matrix. In the mid-1970s, it became possible to identify and quantify mRNAs from higher living organisms using translation in reticulocyte lysate. A few years later, the use of radioactive cDNAs as probes made it possible for the quantification of mRNA in various physiological situations using hybridisation in the liquid phase. Gene cloning offered additional tools to measure milk protein mRNAs and also to identify transcription factors. Gene transfer in cultured mammary cells and in animals contributed greatly to these studies. It is now well established that most if not all genes of higher eukaryotes are under the control of multiple distal regulatory elements and that local modifications of the chromatin structure play an essential role in the mechanisms of differentiation from embryos to adults. The technique, known as ChIP (chromatin immunoprecipitation), is being implemented to identify the factors that modify chromatin structure at the milk protein gene level during embryo development, mammogenesis and lactogenesis, including the action of hormones and extracellular matrix. Transgenesis is not just a tool to study gene regulation and function, it is also currently used for various biotechnological applications including the preparation of pharmaceutical proteins in milk. This implies the design of efficient vectors capable of directing the secretion of recombinant proteins in milk at a high concentration. Milk protein gene promoters and long genomic-DNA fragments containing essentially all the regulatory elements of milk protein genes are used to optimise recombinant protein production in milk.Keywords: chromatin, development, promoter, transgenesis IntroductionMilk protein genes are abundantly and specifically expressed in the mammary gland of lactating mammals. Lactation is essential for the development of newborns. Since the domestication of a few ruminants, milk has become an important food for humans. Milk proteins represent 30% of the proteins consumed by humans in developed countries. On the other hand, milk protein genes are among the most intensively expressed genes and they were soon candidates to study the mechanisms of gene expression. For these reasons, biology of lactation has been extensively studied for the last 50 years. The main factors controlling mammary gland development and milk protein gene expression are well known. These factors are oestrogens, prolactin, progesterone, glucocorticoids, insulin-like growth factor-1, placental lactogen and extracellu...

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“…15 During the construction of the lentiviral vectors, it is essential to limit the length of the vector. The viral titer can be improved using cDNA and not complete gene sequences, as well as including a shorter mammary gland-specific promoter region and polyadenylation signal, such as the a-lactalbumin promoter 8 and the bovine growth hormone poly-A 10 sequences. These modifications can improve the viral titer from lentiviral vectors.…”

Section: Vectors Used In the Generation Of Transgenic Animalsmentioning

confidence: 99%

“…The promoter region localized at the 5 0 -UTR (untranslated region) of the gene of interest, including tissue-specific enhancers for the mammary gland and the first non-coding exons and introns, is variable in size and dependent of the promoter used. Bovine a-lactalbumin and b-lactoglobulin promoters have been used with approximately 2.0 kb and 2.8 kb gene sizes, respectively, 8,9 while casein promoters (aS1, aS2 and b) have generally been used for genes from 3.1 kb to 14.2 kb in length. 10,11 Other regulatory elements, such as insulators, have been added upstream of the 5 0 -UTR in the vector construction to ensure high-level and/or position-independent expression of the transgene.…”

Section: Vectors Used In the Generation Of Transgenic Animalsmentioning

confidence: 99%

Transgenic bovine as bioreactors: Challenges and perspectives

et al. 2016

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The use of recombinant proteins has increased in diverse commercial sectors. Various systems for protein production have been used for the optimization of production and functional protein expression. The mammary gland is considered to be a very interesting system for the production of recombinant proteins due to its high level of expression and its ability to perform post-translational modifications. Cows produce large quantities of milk over a long period of lactation, and therefore this species is an important candidate for recombinant protein expression in milk. However, transgenic cows are more difficult to generate due to the inefficiency of transgenic methodologies, the long periods for transgene detection, recombinant protein expression and the fact that only a single calf is obtained at the end of each pregnancy. An increase in efficiency for transgenic methodologies for cattle is a big challenge to overcome. Promising methodologies have been proposed that can help to overcome this obstacle, enabling the use of transgenic cattle as bioreactors for protein production in milk for industry.

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Production of bovine alpha-lactalbumin in the milk of transgenic pigs.

Cited by 79 publications

References 0 publications

Association between a polymorphism of the α-lactalbumin gene and milk production traits in Chinese Holstein cows

Association between a polymorphism of the α-lactalbumin gene and milk production traits in Chinese Holstein cows

Rabbit milk protein genes: from mRNA identification to chromatin structure

Transgenic bovine as bioreactors: Challenges and perspectives

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