NDLI: Temporal and spatial expression of biologically active human factor VIII in the milk of transgenic mice driven by mammary-specific bovine α-lactalbumin regulation sequences

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Temporal and spatial expression of biologically active human factor VIII in the milk of transgenic mice driven by mammary-specific bovine α-lactalbumin regulation sequences

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Transgenic Research : Volume 11, Issue 2, April 2002

Transgenic Research : Volume 11, Issue 1, February 2002

Transgenic Research : Volume 10

Transgenic Research : Volume 9

Transgenic Research : Volume 8

Transgenic Research : Volume 7

Transgenic Research : Volume 6

Temporal and spatial expression of biologically active human factor VIII in the milk of transgenic mice driven by mammary-specific bovine α-lactalbumin regulation sequences

Content Provider	Springer Nature Link
Author	Chen, Chuan Mu Wang, Chih Hong Wu, Shinn Chih Lin, Chih Cheng Lin, Shwu Hwa Cheng, Winston T.K.
Copyright Year	2002
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 α-lactalbumin and human FVIII cDNA was constructed for microinjection into the pronuclei of newly fertilized mouse eggs. The αLA-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 μg/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.
Starting Page	257
Ending Page	268
Page Count	12
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	11
Issue Number	3
e-ISSN	15739368
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2002-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Plant Sciences Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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Temporal and spatial expression of biologically active human factor VIII in the milk of transgenic mice driven by mammary-specific bovine α-lactalbumin regulation sequences

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