A Dwarf Mouse with Growth Hormone Deficiency Due to Targeted Ablation (Knock Out) of the GHRH Gene

The proliferation of pituitary somatotroph cells and the synthesis and secretion of GH are under the stimulatory control of the hypothalamic peptide GHRH. GHRH is initially synthesized as pre-prohormone and then enzymatically cleaved to its mature form (44 amino acids in humans and 42 in mice). Although mutations in the GHRH receptor cause isolated GH deficiency (IGHD) both in humans and mice, mutations in the GHRH gene have never been described. To determine the consequences of generalized lack of GHRH, JHU researchers have created a mouse with targeted disruption (knockout) of the GHRH gene (GHRHKO) by substituting a portion of the gene that encodes for the initial 14 amino acids of the 1-42 GHRH with a neomycin resistance cassette. This mouse model was used to demonstrate that ablation of the GHRH gene causes IGHD in mice. Description (Set) Proposed Use (Set) The GHRH knock out mouse is an animal model of growth hormone (GH) deficiency (IGHD). It may be used to test therapies for GH deficiency, and to study the effects of lack of GH on growth, organ function, aging and disease processes.

Inventor(s): Salvatori, Roberto

Type of Offer: Licensing

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