Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

Larsen, Marianne O.; Rolin, Bidda

doi:10.1093/ilar.45.3.303

Cited by 168 publications

(124 citation statements)

References 143 publications

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“…Miniature pigs continue to elicit interest as an animal model in the fields of biomedical research [12], transplantation organs [13,14] and disease models [15,16]. However, lack of comprehensive studies on miniature pigs and their cloning has made cloning in them less efficient than in other animals, including domestic pigs.…”

Section: Discussionmentioning

confidence: 99%

Developmental Ability of Miniature Pig Embryos Cloned with Mesenchymal Stem Cells

Lee

Kang

Maeng

et al. 2010

Journal of Reproduction and Development

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Abstract. The present study compared the developmental ability of miniature pig embryos cloned with fetal fibroblasts (FFs), bone marrow-derived mesenchymal stem cells (MSCs) and differentiated (osteocytes, adipocytes and chondrocytes) MSCs. MSCs were isolated from an approximately 1-month-old female miniature pig (T-type, PWG Micro-pig ® , PWG Genetics Korea). MSCs were differentiated into osteocytes, adipocytes and chondrocytes under controlled conditions and characterized by cell surface antigen profile using specific markers. These differentiated or undifferentiated MSCs, as well as FFs of miniature pig, were transferred into enucleated oocytes of domestic pigs. Data from 10 replicates involving 1567 cloned embryos were assessed in terms of developmental rates. The in vitro development rate to the blastocyst stage of embryos cloned with undifferentiated MSCs was significantly (P<0.05) higher than that of embryos cloned with differentiated MSCs and FFs. Surgical transfer of 523 two-cell stage embryos cloned with undifferentiated MSCs into five synchronized domestic pig recipients resulted in 5 cloned miniature pig offspring (1 stillborn and 4 viable) from 2 pregnant recipients. The results imply that MSCs might be multipotent and that they can be used to produce viable cloned miniature pigs that cannot be easily reproduced with differentiated somatic cells. Key words: Animal cloning, Differentiation, Mesenchymal stem cells, Miniature pig, Nuclear transfer (J. Reprod. Dev. 56: [256][257][258][259][260][261][262] 2010) he production of cloned animals by nuclear transfer (NT) has been increasingly studied as a potential approach to tissue and organ xenotransplantation with reduced immunogenicity for endstage organ failure. Several studies have suggested that miniature pigs, rather than nonhuman-primate species, are suitable as a donor animal for human xenotransplantation [1,2] because miniature pigs are superior in terms of similarities in gross anatomy and physiology to humans as well as in terms of ethical issues. The NT efficiency, however, remains relatively low due to abnormalities throughout pre-and post-implantation development regardless of the species or type of donor cell [3]. A number of factors affect NT efficiency, including the NT technical process, activation protocol, recipient oocyte age, cell cycle stage and type of donor cells, which has been implicated in the precise reprogramming of chromatin and genomic imprinting. Among these factors, incomplete selection of donor cells has also been considered a prime cause for NT inefficiency.Transfer of embryonic stem (ES) cells to produce cloned embryos has resulted in consistently higher numbers of viable offspring compared with somatic cells in mice [4,5]. Moreover, embryos cloned with porcine mesenchymal stem cells (MSCs) and their derivatives along the osteogenic lineage give rise to an increase in the rate of preimplantation development compared with adult fibroblasts [6]. Our previous study on gene expression profiles demonstrated that some ge...

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Section: Discussionmentioning

confidence: 99%

Developmental Ability of Miniature Pig Embryos Cloned with Mesenchymal Stem Cells

Lee

Kang

Maeng

et al. 2010

Journal of Reproduction and Development

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“…Cross-sectional areas (mm 2 ) of approximately 200 muscle fibres were measured with an MOP digiplan analyzer (Kontron, Messgeräte GmbH) on photographs of myofibrillar ATPase-stained ( pH 4.6) transverse sections. 20 The insulin content of biopsy samples from the liver and pancreas was determined by extracting insulin by mixing homogenates with acid-ethanol (0.18 mmol/L HCl in 96% ethanol) overnight at 48C.…”

Section: Tissue Analysesmentioning

confidence: 99%

Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism

et al. 2009

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Streptozotocin (STZ) given intravenously destroys pancreatic beta cells and is widely used in animal models to mimic type 1 diabetes. The effects of STZ on the clinical state of health and metabolism were studied in six high health certified domestic pigs weighing 19 + 1.3 kg at the start of the experiment. A single STZ dose of 150 mg/kg of body weight successfully induced hyperglycaemia and alterations in amino acid metabolism. Within 9 h after STZ administration, the blood glucose values fell from 5.4 -7.5 mmol/L to 0.8 -2.2 mmol/L. Hypoglycaemia was treated with 0.5 g glucose/kg body weight. In all pigs, hyperglycaemia was produced 24 h after STZ treatment, and 3 days after STZ injection, the glucose concentration was .25 mmol/L. Mean C-peptide concentration was 0.25 + 0.16 mg/L since 2 days after STZ injection until the end of the study. The serum concentration of the branched-chain amino acids (BCAA) increased four-fold, and alanine and taurine decreased by approximately 70% and 50%, respectively, after STZ treatment. All but one pig remained brisk and the physical examination was normal except for a retarded growth rate and a reduction of the skeletal muscle. At the end of the study, the pigs were moderately emaciated. Postmortem examination confirmed muscle wasting and a reduction of abdominal and subcutaneous fat. In conclusion, STZ-induced diabetes in pigs fulfils the requirements for a good animal model for type 1 diabetes with respect to clinical signs of the disease and alterations in the carbohydrate and amino acid metabolism. Reliable and reproducible animal models are of great importance in diabetes research. Rodent models are widely used, 1 and pigs are suitable when large animal models are required. 2 A pig model can be valuable when repeated biopsies and blood samples are required, and in studies concerning possible therapeutic perspectives such as transplantation of islets.Since spontaneous diabetes is extremely rare in pigs, the disease has to be induced either surgically by pancreatectomy 3,4 or chemically. 5 In Swedish Landrace pigs, i.v. injection of a single dose of 100-150 mg streptozotocin (STZ) has been shown to be a safe procedure for inducing type 1 diabetes. 3Diabetic illness not only affects the carbohydrate and lipid metabolism (reviewed by Taylor and Agius 6 ) but also alters the metabolism of protein. In rats, STZ-induced diabetes has been found to result in a decrease in the rate of protein synthesis and an increase in its degradation. Further, elevations of branched-chain amino acids (BCAAs, i.e. leucine, isoleucine and valine) and decreases in the concentrations of glutamate, glutamine, alanine, glycine, proline, serine and threonine were observed in the blood.

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“…Although rat preadipocytes and http://bmbreports.org BMB reports adipocytes lines are commonly used in obesity studies, it has been suggested that porcine preadipocytes are a better model for the study of obesity and its related disorders because porcine preadipocytes possess higher lipogenic capacity and similar lipogenic patterns to human adipocytes (21)(22)(23). Fernandez reported that guinea pigs could be used as models to study hepatic cholesterol and lipoprotein metabolism (24).…”

Section: Introductionmentioning

confidence: 99%

β-catenin protein utilized by Tumour necrosis factor-α in porcine preadipocytes to suppress differentiation

Luο

Li²,

Liu³

et al. 2009

BMB Reports

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Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

Cited by 168 publications

References 143 publications

Developmental Ability of Miniature Pig Embryos Cloned with Mesenchymal Stem Cells

Developmental Ability of Miniature Pig Embryos Cloned with Mesenchymal Stem Cells

Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism

β-catenin protein utilized by Tumour necrosis factor-α in porcine preadipocytes to suppress differentiation

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