Expression of human lactoferrin in milk of transgenic mice

Platenburg, Gerard; Kootwijk, E.; Kooiman, P M; Woloshuk, Shelley L.; Nuijens, Jan H.; Krimpenfort, Paul; Pieper, Frank; Boer, H. H.; Strijker, R.

doi:10.1007/bf01974087

Cited by 102 publications

(60 citation statements)

References 36 publications

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“…The highest amount of pLF (106 mg/L) was found in progenies of mouse line Tg-pLF-33; this high level of pLF production was stably maintained through 10 generations. The pLF level in progenies of line 33 was significantly higher than the levels found in the human LF transgenic mice reported previously (25).…”

Section: Discussioncontrasting

confidence: 70%

Recombinant Porcine Lactoferrin Expressed in the Milk of Transgenic Mice Enhances Offspring Growth Performance

Chen

Yen

et al. 2007

J. Agric. Food Chem.

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The European Commission has proposed a permanent ban on the use of antibiotics as an ingredient in animal feed to promote growth. Lactoferrin is a globular multifunctional protein that has been shown to play a role in iron absorption and to have antimicrobial and anti-inflammatory activities. Therefore, lactoferrin may serve as a nontherapeutic alternative to antibiotics in livestock husbandry. As a pilot study toward this goal, transgenic mice have been generated harboring a porcine lactoferrin (pLF) gene driven by the mammary gland-specific promoter of the bovine R-lactalbumin (RLA) gene. The RLA-pLF hybrid gene was confirmed to have been successfully integrated and transmitted stably through the germ-line in 9 (5 females and 4 males) of 14 transgenic founders. In the female progenies of six lines analyzed, the transgene copy numbers ranged from 1 to 20 with 1-4 integration sites. Significant levels of pLF protein in milk ranging from 40 to 106 µg/mL with physical characteristics similar to those of native pLF in sow's milk were achieved in three of the transgenic lines obtained. Tissue-and stage-specific pLF expressions were restricted to the mammary gland of the transgenic female mice during lactation. It was further demonstrated that the growth performance of animal pups is enhanced by directly feeding the genetically engineered milk containing enriched pLF protein in transgenic mice. Furthermore, this enhanced growth performance in suckling mice was proportional to the concentration of pLF present in milk.

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Section: Discussioncontrasting

confidence: 70%

Recombinant Porcine Lactoferrin Expressed in the Milk of Transgenic Mice Enhances Offspring Growth Performance

Chen

Yen

et al. 2007

J. Agric. Food Chem.

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“…hLf-transgenic mice (line 2261) and wild-type littermates (strain B6CBA) generated as previously described (16,17) were used to establish a colony at Glasgow University (Glasgow, U.K.). For the CIA model, the transgenic mice were backcrossed on to the DBA/1 background and used after six backcrosses.…”

Section: Animalsmentioning

confidence: 99%

Enhanced Th1 Response toStaphylococcus aureusInfection in Human Lactoferrin-Transgenic Mice

Guillén

McInnes

Vaughan

et al. 2002

The Journal of Immunology

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Lactoferrin (Lf) is an iron-binding protein of external secretions and neutrophil secondary granules with antimicrobial and immunomodulatory activities. To further define these properties of Lf, we have investigated the response to Staphylococcus aureus infection in transgenic mice carrying a functional human Lf gene. The transgenic mice cleared bacteria significantly better than congenic littermates, associated with a trend to reduced incidence of arthritis, septicemia, and mortality. We identified two pathways by which S. aureus clearance was enhanced. First, human Lf directly inhibited the growth of S. aureus LS-1 in vitro. Second, S. aureus-infected transgenic mice exhibited enhanced Th1 immune polarization. Thus, spleen cells from infected transgenic mice produced higher levels of TNF-α and IFN-γ and less IL-5 and IL-10 upon stimulation ex vivo with the exotoxin toxic shock syndrome toxin-1 compared with congenic controls. To confirm that these effects of Lf transgene expression could occur in the absence of live bacterial infection, we also showed that Lf-transgenic DBA/1 mice exhibited enhanced severity of collagen-induced arthritis, an established model of Th1-induced articular inflammation. Higher levels of stainable iron in the spleens of transgenic mice correlated with human Lf distribution, but all other parameters of iron metabolism did not differ between transgenic mice and wild-type littermates. These results demonstrate that human Lf can mediate both antimicrobial and immunomodulatory activities with downstream effects on the outcome of immune pathology in infectious and inflammatory disease.

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“…Many studies have demonstrated that recombinant proteins can be produced in milk, including human IGF-1 (Zinovieva et al, 1998), hGH (Devinoy et al, 1994), human lysozyme (Lee et al, 1998), human lactoferrin (Platenburg et al, 1994), human erythropoietin (Sohn et al, 1999), human parathyroid hormone (Rokkones et al, 1995), and coagulation factor VIII (Chrenek et al, 2007).…”

Section: Use Of Genetically Modified Animals In the Production Of Biomentioning

confidence: 99%

“…Through selective promoters for the mammary gland, such as αs1-casein (Platenburg et al, 1994;Zinovieva et al, 1998) and whey acid protein -WAP (Devinoy et al, 1994;Rokkones et al, 1995), gene expression can be targeted to the mammary gland, with the release of the desired protein in the milk.…”

Section: Use Of Genetically Modified Animals In the Production Of Biomentioning

confidence: 99%

Review article Genetically modified animals for use in research and biotechnology

Chaible¹,

Corat²,

Abdelhay³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Transgenic animals are used extensively in the study of in vivo gene function, as models for human diseases and in the production of biopharmaceuticals. The technology behind obtaining these animals involves molecular biology techniques, cell culture and embryo manipulation; the mouse is the species most widely used as an experimental model. In scientific research, diverse models are available as tools for the elucidation of gene function, such as transgenic animals, knockout and conditional knockout animals, knock-in animals, humanized animals, and knockdown animals. We examined the evolution of the science for the development of these animals, as well as the techniques currently used in obtaining these animal models. We review the phenotypic techniques used for elucidation of alterations caused by genetic modification. We also investigated the role of genetically modified animals in the biotechnology industry, where they promise a revolution in obtaining heterologous proteins through natural secretions, such as milk, increas- ing the scale of production and facilitating purification, thereby lowering the cost of production of hormones, growth factors and enzymes.

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Expression of human lactoferrin in milk of transgenic mice

Cited by 102 publications

References 36 publications

Recombinant Porcine Lactoferrin Expressed in the Milk of Transgenic Mice Enhances Offspring Growth Performance

Recombinant Porcine Lactoferrin Expressed in the Milk of Transgenic Mice Enhances Offspring Growth Performance

Enhanced Th1 Response toStaphylococcus aureusInfection in Human Lactoferrin-Transgenic Mice

Review article Genetically modified animals for use in research and biotechnology

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