328
ECKART SCHOTT, MARTIN PAUL AND DETLEV GANTEN
At the time of this writing only a few protocols for generating transgenics
in larger animal species exist:
• Generation of transgenic rabbits was first reported in 1985 (2), when
Hammer et al. inserted the gene encoding human growth hormone under control of the metallothionein promoter into the rabbit genome.
They obtained an integration-rate of 12.8% (ratio of animals whose genome contained the transgene I all animals that resulted from transfered
oocytes), which is appoximately half of the rate obtained in mice. The
same construct was used by Hammer et al. to generate transgenic sheep,
resulting in the very low integration rate of 1.3%.
• One approach of transgenic technology is to generate animals that secrete large amounts of protein into their milk. Böhler et al. (32) generated
a transgenic rabbit, secreting human interleukin-2 into its milk. Clark et
al. reported on a transgenic sheep, that secreted human factor IX into its
milk (33). The possibility of producing protein in the mammary gland of
transgenic animals has been recently reviewed by Henninghausen et al.
(34).
• Ebert et al. (35) obtained an integration rate of 7% by generating transgenic goats that harbored the gene for the human tissue plasminogen
activator ( tP A) and secreted this protein into their milk.
• In pigs, integration rates of DNA arerather low. Wallet al. (36), for example, obtained an integrationrate of only 1% in transgenic pigs. Swanson et al. (37) generated a pig line which was transgenic for human hemoglobin. The construct was constructed using the control sequence taken from the human ß-globin gene and two copies of the human a 1-globin geneplus a single copy of the ßA-globin gene. Using this protocol,
functional human hemoglobin was produced in the pig.
Transgenie animals in hypertension research: example of an application
A large amount of experimental data is now available for transgenic models
in hypertension research. As of this writing several transgenic rat lines expressing candidate genes for hypertension have been produced. Fora number of reasons that are discussed elsewhere (38), these animals mostly express components of the renin-angiotensin-system (RAS).
Genetic linkage studies have recently demonstrated that the components
of the RAS are associated with hypertension (39, 40). Molecular variants of
angiotensinogen, for example, which result in significant differences in
ECKART SCHOTT, MARTIN PAUL AND DETLEV GANTEN
At the time of this writing only a few protocols for generating transgenics
in larger animal species exist:
• Generation of transgenic rabbits was first reported in 1985 (2), when
Hammer et al. inserted the gene encoding human growth hormone under control of the metallothionein promoter into the rabbit genome.
They obtained an integration-rate of 12.8% (ratio of animals whose genome contained the transgene I all animals that resulted from transfered
oocytes), which is appoximately half of the rate obtained in mice. The
same construct was used by Hammer et al. to generate transgenic sheep,
resulting in the very low integration rate of 1.3%.
• One approach of transgenic technology is to generate animals that secrete large amounts of protein into their milk. Böhler et al. (32) generated
a transgenic rabbit, secreting human interleukin-2 into its milk. Clark et
al. reported on a transgenic sheep, that secreted human factor IX into its
milk (33). The possibility of producing protein in the mammary gland of
transgenic animals has been recently reviewed by Henninghausen et al.
(34).
• Ebert et al. (35) obtained an integration rate of 7% by generating transgenic goats that harbored the gene for the human tissue plasminogen
activator ( tP A) and secreted this protein into their milk.
• In pigs, integration rates of DNA arerather low. Wallet al. (36), for example, obtained an integrationrate of only 1% in transgenic pigs. Swanson et al. (37) generated a pig line which was transgenic for human hemoglobin. The construct was constructed using the control sequence taken from the human ß-globin gene and two copies of the human a 1-globin geneplus a single copy of the ßA-globin gene. Using this protocol,
functional human hemoglobin was produced in the pig.
Transgenie animals in hypertension research: example of an application
A large amount of experimental data is now available for transgenic models
in hypertension research. As of this writing several transgenic rat lines expressing candidate genes for hypertension have been produced. Fora number of reasons that are discussed elsewhere (38), these animals mostly express components of the renin-angiotensin-system (RAS).
Genetic linkage studies have recently demonstrated that the components
of the RAS are associated with hypertension (39, 40). Molecular variants of
angiotensinogen, for example, which result in significant differences in