A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.

@article{Meyer2004ANM,
  title={A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.},
  author={Carola W E Meyer and Dirk Korthaus and Wolfgang Jagla and Emmanuelle Cornali and Johannes Grosse and Helmut Fuchs and Martin Klingenspor and Stephanie Roemheld and Matthias H. Tsch{\"o}p and Gerhard Heldmaier and Martin Hrabě de Angelis and Michael Nehls},
  journal={Endocrinology},
  year={2004},
  volume={145 5},
  pages={
          2531-41
        }
}
The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a-->g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice displaying a less pronounced phenotype. All genotypes are viable and fertile, and the mode of… 
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References

SHOWING 1-10 OF 61 REFERENCES
A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse).
  • Y. Zhou, B. Xu, +9 authors J. Kopchick
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
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.
A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency.
TLDR
Two siblings with IGHD are described due to a new mutation in the GHRHR that disrupts G HRH signaling and leads to GHRH resistance.
Autosomal dominant growth hormone deficiency disrupts secretory vesicles in vitro and in vivo in transgenic mice.
TLDR
A low copy number transgenic line showed a mild effect relatively specific for GH, whereas two severely affected lines with higher transgene copy numbers showed early onset, widespread pituitary damage, macrophage invasion, and multiple hormone deficiencies.
Growth hormone resistance: clinical states and animal models.
TLDR
The characteristics and etiology of Laron syndrome, the animal models proposed, and the insight provided by these disorders into the roles and mechanism of action of GH will be reviewed.
Isolated Growth Hormone Deficiency and the GH-1 Gene: Update 2002
  • G. Binder
  • Biology, Medicine
    Hormone Research in Paediatrics
  • 2002
This short review will focus on the mechanisms which are thought to be directly involved in GH expression and particularly on the monogenetic disorders which were shown to cause isolated growth…
Inhibition of growth hormone (GH) secretion by a mutant GH-I gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner.
TLDR
The synthesis and secretion of GH encoded by the mutant GH-I genes are studied and it is concluded that the dominant negative effect of mutant GH on the secretion of wild-type GH is at least in part responsible for the pathogenesis of IGHD type II.
Isolated GH deficiency with dominant inheritance: new mutations, new insights.
TLDR
The observed discrepancy between the very homogeneous hormone data proving severe GH and IGF-I deficiencies and the high variability of growth failure even within the same family suggests that the onset and predominance of GH-dependent growth during infancy are individually different and modified by as yet unknown factors.
The molecular genetics of growth hormone deficiency
TLDR
This review focuses primarily on the GH1 mutational spectrum and its unusual features, discusses potential mechanisms of mutagenesis and pathogenesis, and examines the correlation between mutant genotype and clinical phenotype.
Dwarf mice produced by genetic ablation of growth hormone-expressing cells.
TLDR
Nearly all somatotropes were absent, as shown by GH immunostaining in the transgenic pituitaries, and a model for the lineal relationships between GH- and PRL-synthesizing cells is proposed.
Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice.
TLDR
The data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH.
...
1
2
3
4
5
...