title: A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse).
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.
authors.affiliation: Edison Biotechnology Institute, Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens 45701, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: B C
authors.initials: BC
authors.lastname: Xu
authors.forename: H G
authors.initials: HG
authors.lastname: Maheshwari
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: M
authors.initials: M
authors.lastname: Reed
authors.forename: M
authors.initials: M
authors.lastname: Lozykowski
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: L
authors.initials: L
authors.lastname: Cataldo
authors.forename: K
authors.initials: K
authors.lastname: Coschigamo
authors.forename: T E
authors.initials: TE
authors.lastname: Wagner
authors.forename: G
authors.initials: G
authors.lastname: Baumann
authors.forename: J J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005298:Fertility / Q000235:genetics; D018390:Gene Targeting; D006130:Growth Disorders / Q000235:genetics*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D013006:Growth Hormone; C051815:somatotropin-binding protein