Transgenic livestock as bioreactors: stable expression of human alpha-1-antitrypsin by a flock of sheep

We have previously described the generation of transgenic sheep expressing human alpha 1-antitrypsin (h alpha 1AT) in their milk. Here, we report the fidelity of transgene transmission and expression by these animals and their progeny. Transgene transmission has been demonstrated in four of six ovin...

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Bibliographic Details
Published in:	Bio/technology (New York, N.Y. 1983) Vol. 11; no. 11; pp. 1263 - 1270
Main Authors:	Carver, A.S, Dalrymple, M.A, Wright, G, Cottom, D.S, Reeves, D.B, Gibson, Y.H, Keenan, J.L, Barrass, J.D, Scott, A.R, Colman, A
Format:	Journal Article
Language:	English
Published:	New York, NY Nature Publications 01-11-1993
Subjects:	alpha 1-Antitrypsin - biosynthesis alpha 1-Antitrypsin - genetics ANIMAL TRANSGENIQUE ANIMALES TRANSGENICOS Animals Animals, Genetically Modified Biological and medical sciences Biotechnology Biotechnology - methods ENZYME INHIBITORS EWE MILK EXPRESION GENICA EXPRESSION DES GENES Female Fundamental and applied biological sciences. Psychology GENE GENE DOSAGE GENE EXPRESSION GENE TRANSFER GENERO HUMANO GENES Genetic engineering GENETIC INHERITANCE Genetic technics GENETIC TRANSFORMATION GENRE HUMAIN HEREDITE HERENCIA GENETICA Humans INHIBIDORES DE ENZIMAS INHIBITEUR D'ENZYME LACTACION LACTATION LAIT DE BREBIS LECHE DE OVEJA Male MANKIND Methods. Procedures. Technologies MICE Milk - metabolism OVIN OVINOS PROTEINAS PROTEINE PROTEINS RATON SECRECION SECRETION SHEEP SOURIS STRUCTURAL GENES TRANSFERENCIA DE GENES TRANSFERT DE GENE TRANSFORMACION GENETICA TRANSFORMATION GENETIQUE TRANSGENIC ANIMALS Transgenic animals and transgenic plants Vertebrata Bioreactor Mammalia Gel electrophoresis Production Transgenic animal Sheep Livestock Artiodactyla Gene expression Ungulata α1-Antitrypsin
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Summary:	We have previously described the generation of transgenic sheep expressing human alpha 1-antitrypsin (h alpha 1AT) in their milk. Here, we report the fidelity of transgene transmission and expression by these animals and their progeny. Transgene transmission has been demonstrated in four of six ovine lines studied. Three of these four lines have exhibited stable transmission of the transgene, whereas the fourth has produced some offspring with reduced copy numbers. Sequential lactations of founder animals has yielded very similar levels of h alpha 1AT protein in milk. Moreover, in one line, derived from a founder male, a flock of seven G1 ewes have yielded comparable levels of h alpha 1AT protein in first and second lactation milk. Two G2 ewes of this line have also produced levels of human protein equivalent to their mother. Although the inheritance of the same transgene in mice was reminiscent of the situation in sheep, stable expression was observed in only one or four lines studied. The importance of these observations to the use of transgenic livestock as bioreactors for the production of human proteins is discussed.
Bibliography:	L10 9440716 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0733-222X 2331-3684
DOI:	10.1038/nbt1193-1263