The production of transgenic domestic livestock: successes, failures and the need for nuclear transfer

1998 ◽  
Vol 10 (8) ◽  
pp. 659 ◽  
Author(s):  
Kevin A. Ward ◽  
Bruce W. Brown
Keyword(s):  
Growth Hormone ◽  
Recombinant Dna ◽  
Genetic Manipulation ◽  
Good Health ◽  
Practical Method ◽  
Intermediary Metabolism ◽  
Growth Hormone Gene ◽  
Metallothionein Promoter ◽  
Domestic Livestock ◽  
Species Specific

The direct transfer of recombinant DNA to embryos is conceptually a powerful method for the manipulation of the genetic potential of domestic animals, but in practice the technology has yet to fulfil its promise. In this paper, two examples are given of research utilising direct genetic manipulation, both of which are aimed at increasing aspects of productivity in sheep. The first of these involves the modification of the growth hormone status of sheep by the use of the ovine growth hormone gene, the regulation of which has been altered by the use of an ovine metallothionein promoter. While there has been a large amount of research already conducted in this area by many groups, our recent results provide one of the first demonstrations that this approach can increase the growth rates of sheep while maintaining the animals in good health. The second project involves the modification of intermediary metabolism in sheep by the introduction of the cysteine biosynthetic pathway. The results to date demonstrate that it is possible to change intermediary metabolism in animals using our approach but that there are species-specific requirements that must be satisfied in order to make the approach a practical method for improving animal productivity.

PROSPECTS FOR BIOTECHNOLOGY IN ANIMAL PRODUCTION

1988 ◽  
pp. 63-65
Author(s):  
J.W. Forrest ◽  
T.E. Broad
Keyword(s):  
Growth Hormone ◽  
Biosynthetic Pathway ◽  
Recombinant Dna ◽  
Transgenic Animal ◽  
Growth Hormone Gene ◽  
Live Births ◽  
Wool Growth ◽  
Domestic Livestock ◽  
Rat Growth ◽  
Multiple Copies

Through recent advances in molecular and reproductive biology selected genes from one animal or species can be inserted into another animal's genome to produce a 'transgenic' animal. Striking increases have been achieved in the rate of growth of mice containing additional copies of the rat growth hormone gene. Such results raised the possibility of using similar techniques to modify the expression of existing genes and introduce novel gene(s) into domestic livestock for improved productivity. The introduction of multiple copies of the growth hormone genes into pig embryos has resulted in live births of pigs that grew 10-20X larger and reached market weight three weeks earlier than litter-mates. The introduced genes were passed from generation to generation. In sheep cysteine supplementation into the abomasum produced at 10.20% increase in wool growth rate. Genes responsible for cysteine biosynthesis have been isolated from yeast, and a modified gene suitable for expression in sheep produced. By engineering the cysteine biosynthetic pathway into the sheep genome there is scope to considerably increase wool production. Keywords: gene transfer, transgenesis. recombinant DNA, embryo manipulation.

Introduction of a porcine growth hormone fusion gene into transgenic pigs promotes growth

1988 ◽  
Vol 90 (2) ◽  
pp. 295-300
Author(s):  
P.D. Vize ◽  
A.E. Michalska ◽  
R. Ashman ◽  
B. Lloyd ◽  
B.A. Stone ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Fusion Gene ◽  
Transgenic Animals ◽  
Growth Hormone Gene ◽  
Gene Sequences ◽  
Transgenic Pigs ◽  
Gene Construct ◽  
Metallothionein Promoter

Six transgenic pigs have been produced by microinjecting a human metallothionein promoter/porcine growth hormone gene construct into the pronuclei of fertilized eggs which were transferred to synchronized recipient sows. The resulting transgenic animals contained between 0.5 and 15 copies of the gene construct per cell, and at least one of the animals expressed the introduced gene and grew at an increased rate compared to both transgenic and non-transgenic littermates. Some of the transgenic animals that did not appear to grow at increased rates were found to contain rearranged gene sequences. Two of the transgenic pigs have been shown to pass on the introduced genes to their offspring.

scholarly journals Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future

2021 ◽  
Vol 12 ◽  
Author(s):  
Evan Graber ◽  
Edward O. Reiter ◽  
Alan D. Rogol
Keyword(s):  
Growth Hormone ◽  
Recombinant Dna ◽  
Human Growth ◽  
Enzymatic Digestion ◽  
Laboratory Animals ◽  
Extraction And Purification ◽  
The Future ◽  
Species Specific ◽  
Large Animals ◽  
Pharmacologic Agents

Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic surgery and multiple pharmacologic agents. Virtually at the same time experiments with the removal of the pituitary from laboratory animals noted the slowing or stopping of linear growth and then over a few decades the extraction and purification of a protein within the anterior pituitary that restored, partially or in full, the animal’s growth. Human growth hormone was purified decades after those from large animals and it was noted that it was species specific, that is, only primate growth hormone was metabolically active in primates. That was quite unlike the beef and pork insulins which revolutionized the care of children with diabetes mellitus. A number of studies included mild enzymatic digestion of beef growth hormone to determine if those “cores” had biologic activity in primates and man. Tantalizing data showed minimal but variable metabolic efficacy leading to the “active core” hypothesis, for these smaller peptides would be amenable to peptide synthesis in the time before recombinant DNA. Recombinant DNA changed the landscape remarkably promising nearly unlimited quantities of metabolically active hormone. Eight indications for therapeutic use have been approved by the Food and Drug Administration and a large number of clinical trials have been undertaken in multiple other conditions for which short stature in childhood is a sign. The future predicts other clinical indications for growth hormone therapy (and perhaps other components of the GH?IGF-1 axis), longer-acting analogues and perhaps a more physiologic method of administration as virtually all methods at present are far from physiologic.

A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio

2020 ◽  
Vol 33 (6) ◽  
pp. 735-742
Author(s):  
Meliha Demiral ◽  
Mehmet Salih Karaca ◽  
Edip Unal ◽  
Birsen Baysal ◽  
Rıza Taner Baran ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Cost Benefit ◽  
Practical Method ◽  
Hormone Deficiency ◽  
Small Scale ◽  
Pituitary Hormone ◽  
Clinical Value ◽  
Pubertal Status ◽  
Sensitive Tool

AbstractBackgroundsLimitations in the evaluation of the pituitary size and changes according to pubertal status make its validity questionable. Recently, in a small-scale study, pons ratio (PR) has been suggested as a more sensitive tool for diagnosis and etiological evaluation of growth hormone deficiency (GHD). The aim of the study is to evaluate the diagnostic value of PR in the diagnosis of GHD.MethodsWe retrospectively evaluated the pituitary magnetic resonance imaging (MRI) of 133 patients with a diagnosis of GHD. Primary axis (PA) was assigned as a line crossing the mid-sagittal dorsum sella and fourth ventricle. PR was defined as the pons height above the PA divided by total pons height. The PR of patients with GHD was compared to subjects without GHD.ResultsStudy included 133 patients with GHD and 47 controls. In total, 121 (91%) patients had isolated GHD and 12 (9%) patients had multiple pituitary hormone deficiency. The PR of the patient group (mean: 0.32 ± 0.89; range: 0.14–0.63) was significantly higher than controls (mean: 0.26 ± 0.067; range 0.19–0.44) (p: 0.000). The optimal cut-off value of PR for GHD diagnosis was 0.27 (sensitivity 71% specificity 56%). There was a negative correlation between anterior pituitary height (APH)-SDS and PR (p: 0.002; r: −0.27). APH was increased, but PR remained unchanged in pubertal patients (p: 0.089).ConclusionsPR measurement is a noninvasive, practical method with a cost-benefit clinical value. As it is not affected by pubertal status, PR is potentially a more sensitive tool for evaluation of pituitary gland in GHD patients compared to APH.

scholarly journals The human growth hormone gene contains both positive and negative control elements.

1988 ◽  
Vol 263 (11) ◽  
pp. 5005-5007 ◽  
Author(s):  
L N Peritz ◽  
E J Fodor ◽  
D W Silversides ◽  
P A Cattini ◽  
J D Baxter ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Negative Control ◽  
Growth Hormone Gene ◽  
Human Growth Hormone Gene

scholarly journals Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1128
Author(s):  
Marilena Nakaguma ◽  
Nathalia Garcia Bianchi Pereira Ferreira ◽  
Anna Flavia Figueredo Benedetti ◽  
Mariana Cotarelli Madi ◽  
Juliana Moreira Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Male Patient ◽  
Missense Variant ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Incomplete Penetrance ◽  
Growth Hormone Gene ◽  
Posterior Lobe ◽  
Allelic Variants ◽  
Phenotypic Spectrum

We report four allelic variants (three novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p.Phe 57Leufs*43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A hemizygous SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). This variant was previously reported in a patient with severe holoprosencephaly and shown to affect TGIF1 function. A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in three genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.

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