ArticleTransgenic research2002
Temporal and spatial expression of biologically active human factor VIII in the milk of transgenic mice driven by mammary-specific bovine alpha-lactalbumin regulation sequences.
Article in Transgenic research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 36 citations in OpenAlex.
- Novel Coagulation Factor VIII Gene Therapy in a Mouse Model of Hemophilia A by Lipid-Coated FeBiomedicines · 2021Article
- Investigation of hFVIII production in mammary glands of transgenic mice.Monoclonal antibodies in immunodiagnosis and immunotherapy · 2014Article
- Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.BioMed research international · 2014Article
- Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2013Article
- Blood Clotting Factor VIII: From Evolution to Therapy.Acta naturae · 2013Article
- Functional factor VIII made with von Willebrand factor at high levels in transgenic milk.Journal of thrombosis and haemostasis : JTH · 2011Article
- Gingyo-san enhances immunity and potentiates infectious bursal disease vaccination.Evidence-based complementary and alternative medicine : eCAM · 2011Article
- Granzyme G is expressed in the two-cell stage mouse embryo and is required for the maternal-zygotic transition.BMC developmental biology · 2010Article
- Expression of recombinant human factor VIII in milk of several generations of transgenic rabbits.Transgenic research · 2007Article
- Dynamic control of oligosaccharide modification in the mammary gland: linking recombinant human erythropoietin functional analysis of transgenic mouse milk-derived hEPO.Transgenic research · 2006Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. Recent developments indicate that manipulating milk composition using transgenesis has focused mainly on the mammary gland as a bioreactor to produce pharmaceuticals. In the present study, a hybrid gene containing bovine alpha-lactalbumin and human FVIII cDNA was constructed for microinjection into the pronuclei of newly fertilized mouse eggs. The alphaLA-hFVIII hybrid gene was confirmed to be successfully integrated and stably germ-line transmitted in 12 (seven females/five males) lines. Western-blot analysis of milk samples obtained from eight of the transgenic founders and F1 offspring indicated that the recombinant hFVIII was secreted into the milk of the transgenic mice. The concentrations of rFVIII ranged from 7.0 to 50.2 microg/ml, over 35-200-fold higher than that in normal human plasma. Up to 13.4 U/ml of rFVIII was detected in an assay in which rFVIII restored normal clotting activity to FVIII-deficient human plasma.
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