Abstract
Repression of GH signaling: One extended life to live!
Highlights
We have generated two independent dwarf mouse lines with decreased GH action; only one has extended longevity
The expressed transgene is a mutated bovine GH gene in which the codon for the smaller glycine amino acid at position 119 is replaced with a larger amino acid, which causes steric hindrance when it interacts with the GHR resulting in a classical receptor antagonist [4]
Regardless, comparing the phenotype of growth hormone receptor antagonist (GHA) mice with other long-lived lines, such as GHR-/- mice, should reveal the most important traits caused by reduced GH action that are responsible for lifespan extension
Summary
We have generated two independent dwarf mouse lines with decreased GH action; only one has extended longevity. GHR-/- mice are completely resistance to GH action, which causes a reproducible extension of lifespan regardless of the genetic strain of mice [1 ,2] and is officially recognized as the longest-lived laboratory mouse (http://methuselahfoundation.org/). In 1991, our laboratory first described another dwarf mouse line that expresses a growth hormone receptor antagonist (GHA) transgene [3].
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