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5-Animals: New generation of GE-pigs with extra growth hormon genes announced



----------------------------- GENET-news -----------------------------

TITLE:  Modified genes stimulate pig growth
SOURCE: ISB News Report - March 2000
        by Eric A. Wong
DATE:   March 3, 2000

-------------------- archive: http://www.gene.ch/ --------------------


Modified genes stimulate pig growth

The growth hormone, secreted by the pituitary, plays a key role in 
regulating growth and metabolism in mammals. Under normal conditions, 
growth hormone (GH) secretion is regulated by two hypothalamic 
hormones. Growth hormone releasing hormone (GHRH) stimulates GH 
secretion, while somatostatin inhibits GH secretion. The secreted GH 
induces the synthesis and secretion of insulin-like growth factor-I 
(IGF-I) mainly from the liver into the blood. IGF-I then acts at a 
number of target tissues to stimulate growth.

Transgenesis has been previously investigated as a method of 
increasing growth rate in pigs. In the late 1980s, transgenic pigs 
containing a human or bovine GH gene under the control of the liver-
specific metallothionein promoter showed increased weight gain, 
increased feed efficiency, and decreased fat deposition. A number of 
pathologies, however, were also observed in these GH-transgenic pigs 
such as gastric ulcers, arthritic joints, and decreased libido. In an 
attempt to circumvent these problems, transgenic pigs secreting human 
GHRH from the liver were developed. No effect was observed, however, 
in these GHRH-transgenic pigs, perhaps due to breakdown of the GHRH 
in the circulation by peptidases.

A different approach for overexpression of GHRH in pigs is reported 
in the December 1999 issue of Nature Biotechnology. Researchers at 
Baylor College of Medicine and Penn State combined the technologies 
of site-directed mutagenesis and electrogene therapy (direct plasmid 
gene transfer plus electroporation) to express a protease-resistant 
GHRH in transfected muscle tissue of pigs.

A DNA construct containing the porcine GHRH gene under the control of 
a muscle-specific synthetic promoter was constructed. A single 10 mg 
dose of this plasmid was injected intramuscularly into three week old 
piglets. To improve the efficiency of cellular uptake of the plasmid 
DNA, a pair of electrodes were then inserted into the DNA injection 
site to deliver electric pulses. These injected pigs showed a two- to 
four-fold increase in serum GHRH, an increase in GH secretion, and a 
three- to six-fold increase in serum IGF-I. The increases in serum 
GHRH and IGF-I were maintained for over 60 days after injection.

The myogenic overexpression of porcine GHRH increased growth over 65 
days. Pigs injected with the modified porcine GHRH on average were 
42% heavier than controls at 62 days (42 kg versus 29 kg). Body 
composition studies showed a proportional increase of all body 
components in GHRH injected animals. No signs of organomegaly or 
associated pathology were observed. Feed conversion in GHRH injected 
animals improved by 20% over controls. A significant reduction in 
serum urea concentration was reported indicating a decrease in amino 
acid catabolism.

These results demonstrate a promising, simple, and inexpensive 
approach for increasing growth rate in swine with no apparent adverse 
side effects. Only a single injection of naked plasmid DNA encoding a 
modified GHRH gene into muscle is effective. It will be interesting 
to see if this increase in growth rate can persist for six months 
until pigs reach the typical market weight of 110 to 120 kg.

Source
Draghia-Akli R et al. 1999. Myogenic expression of an injectable 
protease-resistant growth hormone-releasing hormone augments long 
term growth in pigs. Nature Biotechnology 17: 1179-1183.

Eric A. Wong
Department of Animal and Poultry Sciences
Virginia Tech
ewong@vt.edu 

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