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.
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Authors | Y Zhou, B C Xu, H G Maheshwari, L He, M Reed, M Lozykowski, S Okada, L Cataldo, K Coschigamo, T E Wagner, G Baumann, J J Kopchick |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 94
Issue 24
Pg. 13215-20
(Nov 25 1997)
ISSN: 0027-8424 [Print] United States |
PMID | 9371826
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carrier Proteins
- Receptors, Somatotropin
- Growth Hormone
- somatotropin-binding protein
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Topics |
- Animals
- Carrier Proteins
(genetics, metabolism)
- Disease Models, Animal
- Fertility
(genetics)
- Gene Targeting
- Growth Disorders
(genetics)
- Growth Hormone
(metabolism)
- Humans
- Mice
- Mice, Knockout
- Receptors, Somatotropin
(genetics, metabolism)
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