A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse)
Yihua Zhou,Bixiong C. Xu,Hiralal G. Maheshwari,Li He,Michael Reed,Maria Lozykowski,Shigeru Okada,Lori Cataldo,Karen Coschigamo,Thomas Wagner,Gerhard Baumann,John J. Kopchick +11 more
TLDR
The findings indicate that the G HR/BP-deficient mouse (Laron mouse) is a suitable model for human Laron syndrome that will prove useful for the elucidation of many aspects of GHR/BP function that cannot be obtained in humans.Abstract:
Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported in mammals other than humans. Many aspects of GHR dysfunction remain unknown because of ethical and practical limitations in studying humans. To create a mammalian model for this disease, we generated mice bearing a disrupted GHR/binding protein (GHR/BP) gene through a homologous gene targeting approach. Homozygous GHR/BP knockout mice showed severe postnatal growth retardation, proportionate dwarfism, absence of the GHR and GH binding protein, greatly decreased serum insulin-like growth factor I and elevated serum GH concentrations. These characteristics represent the phenotype typical of individuals with Laron syndrome. Animals heterozygous for the GHR/BP defect show only minimal growth impairment but have an intermediate biochemical phenotype, with decreased GHR and GH binding protein expression and slightly diminished insulin-like growth factor I levels. These findings indicate that the GHR/BP-deficient mouse (Laron mouse) is a suitable model for human Laron syndrome that will prove useful for the elucidation of many aspects of GHR/BP function that cannot be obtained in humans.read more
Citations
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Stat5a and Stat5b Proteins Have Essential and Nonessential, or Redundant, Roles in Cytokine Responses
Stephan Teglund,Catriona McKay,Erin G. Schuetz,Jan M. van Deursen,Dimitrios J. Stravopodis,Demin Wang,Michael Brown,Sara Bodner,Gerard Grosveld,James N. Ihle,James N. Ihle +10 more
TL;DR: The phenotypes of the mice demonstrate an essential, and often redundant, role for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin.
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Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human
TL;DR: The pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis is reviewed and it is proposed that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints.
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The Somatomedin Hypothesis: 2001
TL;DR: In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF- I levels are normal.
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Androgens and bone
Dirk Vanderschueren,Liesbeth Vandenput,Steven Boonen,Marie K. Lindberg,Roger Bouillon,Claes Ohlsson +5 more
TL;DR: Observations in androgen-resistant animals clearly demonstrated that the sexual dimorphism of bone depends on the presence of a functional androgen receptor, and optimal peak bone mass seems related to an appropriately timed androgen secretion.
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Growth Hormone, Insulin-Like Growth Factors, and the Skeleton
TL;DR: GH and IGF-I secretion are decreased in aging individuals, and abnormalities in the GH/IGF-I axis play a role in the pathogenesis of the osteoporosis of anorexia nervosa and after glucocorticoid exposure.
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