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      Is Open Access

      Completion of the swine genome will simplify the production of swine as a large animal biomedical model

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          Abstract

          Background

          Anatomic and physiological similarities to the human make swine an excellent large animal model for human health and disease.

          Methods

          Cloning from a modified somatic cell, which can be determined in cells prior to making the animal, is the only method available for the production of targeted modifications in swine.

          Results

          Since some strains of swine are similar in size to humans, technologies that have been developed for swine can be readily adapted to humans and vice versa. Here the importance of swine as a biomedical model, current technologies to produce genetically enhanced swine, current biomedical models, and how the completion of the swine genome will promote swine as a biomedical model are discussed.

          Conclusions

          The completion of the swine genome will enhance the continued use and development of swine as models of human health, syndromes and conditions.

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          Most cited references96

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          Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.

          Overlapping complementary DNA clones were isolated from epithelial cell libraries with a genomic DNA segment containing a portion of the putative cystic fibrosis (CF) locus, which is on chromosome 7. Transcripts, approximately 6500 nucleotides in size, were detectable in the tissues affected in patients with CF. The predicted protein consists of two similar motifs, each with (i) a domain having properties consistent with membrane association and (ii) a domain believed to be involved in ATP (adenosine triphosphate) binding. A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
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            Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.

            In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.
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              Altering the genome by homologous recombination.

              M Capecchi (1989)
              Homologous recombination between DNA sequences residing in the chromosome and newly introduced, cloned DNA sequences (gene targeting) allows the transfer of any modification of the cloned gene into the genome of a living cell. This article discusses the current status of gene targeting with particular emphasis on germ line modification of the mouse genome, and describes the different methods so far employed to identify those rare embryonic stem cells in which the desired targeting event has occurred.
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                Author and article information

                Journal
                BMC Med Genomics
                BMC Med Genomics
                BMC Medical Genomics
                BioMed Central
                1755-8794
                2012
                15 November 2012
                : 5
                : 55
                Affiliations
                [1 ]National Swine Resource and Research Center, University of Missouri, 920 E. Campus Dr, Columbia, MO, 65211, USA
                [2 ]Molecular Animal Breeding and Biotechnology, Department of Veterinary Sciences and Laboratory for Functional Genome Analysis, Feoder-Lynen-Strasse 250, Munich, 81377, Germany
                [3 ]Center for Development of Advanced Technology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, 329-0498, Japan
                [4 ]Laboratory of Developmental Engineering, Meiji University, 1-1-1 Higashimita, Tama, Kawasaki, 214-8571, Japan
                Article
                1755-8794-5-55
                10.1186/1755-8794-5-55
                3499190
                23151353
                0b49f638-2474-43d2-91b4-1e8a864e1fe0
                Copyright ©2012 Walters et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 June 2011
                : 28 October 2011
                Categories
                Review

                Genetics
                genetically engineered,genomic,human diseases,pig,biomedical model
                Genetics
                genetically engineered, genomic, human diseases, pig, biomedical model

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