Transgenic Wuzhishan minipigs designed to express a dominant-negative porcine growth hormone receptor display small stature and a perturbed insulin/IGF-1 pathway.
Growth hormone (GH) is an anabolic mitogen with widespread influence on cellular growth and differentiation as well as on glucose and lipid metabolism. GH binding to the growth hormone receptor (GHR) on hepatocytes prompts expression of insulin growth factor I (IGF-1) involved in nutritionally induced compensatory hyperplasia of pancreatic β-cell islets and insulin release. A prolonged hyperactivity of the IGF-1/insulin axis in the face of insulinotropic nutrition, on the other hand, can lead to collapse of the pancreatic islets and glucose intolerance. Individuals with Laron syndrome carry mutations in the GHR gene resulting in severe congenital IGF-1 deficiency and elevated GH serum levels leading to short stature as well as perturbed lipid and glucose metabolism. However, these individuals enjoy a reduced prevalence of acne, cancer and possibly diabetes. Minipigs have become important biomedical models for human conditions due to similarities in organ anatomy, physiology, and metabolism relative to humans. The purpose of this study was to generate transgenic Wuzhishan minipigs by handmade cloning with impaired systemic GHR activity and assess their growth profile and glucose metabolism. Transgenic minipigs featuring overexpression of a dominant-negative porcine GHR (GHR(dm)) presented postnatal growth retardation and proportionate dwarfism. Molecular changes included elevated GH serum levels and mild hyperglycemia. We believe that this model may prove valuable in the study of GH functions in relation to cancer, diabetes and longevity.
BGI-Shenzhen, Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Feida
F
Li
BGI-Shenzhen, Shenzhen, 518083, China.|BGI Ark Biotechnology (BAB), Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Yong
Y
Li
BGI-Shenzhen, Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Huan
H
Liu
BGI-Shenzhen, Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Xingju
X
Zhang
BGI-Shenzhen, Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Chuxin
C
Liu
BGI-Shenzhen, Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Kai
K
Tian
BGI-Shenzhen, Shenzhen, 518083, China.|Department of Biomedicine, Aarhus University, Wilhelm Meyers allé 1240, 8000, Aarhus C, Denmark.
Lars
L
Bolund
BGI Ark Biotechnology (BAB), Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Hongwei
H
Dou
BGI Ark Biotechnology (BAB), Shenzhen, 518083, China.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
Wenxian
W
Yang
BGI-Shenzhen, Shenzhen, 518083, China.
Huanming
H
Yang
Department of Biomedicine, Aarhus University, Wilhelm Meyers allé 1240, 8000, Aarhus C, Denmark. nhs@clin.au.dk.
Nicklas Heine
NH
Staunstrup
BGI-Shenzhen, Shenzhen, 518083, China. duyt@genomics.cn.|BGI Ark Biotechnology (BAB), Shenzhen, 518083, China. duyt@genomics.cn.|ShenZhen Engineering Laboratory for Genomics-Assisted Animal Breeding, BGI-Shenzhen, 8F Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China. duyt@genomics.cn.
Yutao
Y
Du
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007328:Insulin / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D046150:Laron Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature
D007328:Insulin; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I
Growth hormone; Laron syndrome; Metabolic syndrome; Pig cloning