GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289769/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289769GEOGSEfalseGH-resistant (Laron) mice: gene therapy with a liver-specific GH receptor causes unbalanced upregulation of female-biased and growth-related genesGrowth hormone (GH) receptor (GHR) mutations give rise to GH-resistance (Laron syndrome). We previously treated GH-resistant Ghr-/- mice (Laron mice) with adeno-associated virus (AAV) delivering mouse (m)Ghr controlled by a constitutively active liver-specific promoter (HLP). A single injection of AAV-HLP-mGHR resulted in a significant but limited increase in body length and weight, consistent with studies of IGF-1 treatment in humans and mice. Here, we performed RNA-seq on male and female mouse livers comprising the following groups: GHR+/+ (wild-type), GHR-/- (Laron), AAV-HLP-mGHR-treated GHR-/- (treatment group), and AAV-HLP-Luc (Luciferase)-treated GHR-/- (control group). Only four genes showed significant differential expression in GHR -/- mouse liver following Luciferase vector treatment, indicating minimal effect of the AAV-HLP vector. AAV-HLP-mGHR stimulated significant expression changes in 448 genes compared to AAV-HLP-Luc control, substantially fewer than the 2781 genes whose expression was altered in GHR-/- compared to GHR+/+. AAV-HLP-mGHR treatment induced the GH-responsive IGF signaling genes Igf1 and Igfals ~16-fold compared to AAV-HLP-Luc control, but only to 40–45% of GHR+/+ liver levels. The treatment also upregulated a small subset of genes beyond GHR+/+ expression levels (p-adj < 0.05), including the proto-oncogenes Ascl1, Tmprss4, and others. Finally, genes dysregulated upon GHR loss and upregulated in livers of AAV-HLP-mGHR-treated mice were significantly enriched for sex-biased genes, consistent with the major role of GH and GHR in regulating liver sex differences. While gene replacement therapy is a potential therapy for Laron syndrome, an unregulated constitutively active promoter may drive unexpected and unbalanced changes in liver gene expression that will require monitoring.2026/06/18GSE289769GSM8798239GSM8798238GSM8798249GSM8798235GSM8798246GSM8798245GSM8798234GSM8798248GSM8798237GSM8798236GSM8798247GSM8798231GSM8798253GSM8798242GSM8798241GSM8798252GSM8798233GSM8798244GSM8798254GSM8798243GSM8798232GSM8798251GSM8798240GSM879825024247289769Mus musculus[42290866]