Mice with Heterozygous Deletion of Exon 3 in the <i>Gh</i> Gene Demonstrate Growth Retardation Caused by Reduced <i>Ghrhr</i> mRNA.

ABSTRACT: Isolated Growth Hormone Deficiency Type 2 (IGHD2) is caused by a heterozygous splice site variant in intron 3 of the GH1 gene. The resulting exon 3-skipped growth hormone (Δ3 GH), produced from the mutated allele, exerts a dominant-negative effect, leading to growth hormone (GH) deficiency. However, the precise molecular mechanisms underlying this effect remain poorly understood. While several model murine models expressing human Δ3 GH have been developed, no IGHD2 mouse models featuring variants in the endogenous Gh gene currently exist. We generated a mouse model (Gh^+/Δ3) with a heterozygous deletion of exon 3 in the Gh gene using CRISPR/Cas9 system. The Gh^+/Δ3 model exhibited GH deficiency caused by a dominant-negative effect at t

SUBMITTER: Ariyasu D 

PROVIDER: S-EPMC11817076 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature