Mouse models implicate STAT5–IGF1 pathway in PDGFRb-driven connective tissue overgrowth
A bioRxiv preprint identifies the GH–STAT5–IGF1 signalling axis as a mediator of skeletal and connective tissue overgrowth caused by gain-of-function PDGFRb mutations in Kosaki overgrowth syndrome.
A preprint posted to bioRxiv on 29 August 2026 reports findings from mouse models engineered to carry constitutively activating mutations in platelet-derived growth factor receptor beta (PDGFRb), the gene responsible for the autosomal dominant Kosaki overgrowth syndrome — a rare condition characterised by excessive growth of the skeleton and other connective tissues.
The authors investigated which cell types and downstream signalling pathways mediate the overgrowth phenotype. Normal postnatal skeletal growth depends on pituitary-derived growth hormone (GH), which activates the transcription factor STAT5, which in turn drives expression of insulin-like growth factor 1 (IGF1). The preprint reports that constitutive PDGFRb activation in mouse connective tissue engages this same GH–STAT5–IGF1 axis ectopically, identifying it as a mechanistic driver of the syndrome's overgrowth features.
The findings suggest that the target cell population for pathological PDGFRb signalling lies within the connective tissue compartment rather than in neural or endocrine cells, and that STAT5-dependent IGF1 upregulation is a key molecular step. The authors propose this pathway as a candidate focus for future therapeutic investigation in Kosaki syndrome and potentially related PDGFRb-associated conditions.
This is a preprint and has not undergone peer review. Results from mouse models may not translate directly to human biology.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Kosaki overgrowth syndrome is a rare inherited condition caused by changes in a gene called PDGFRb. People with this condition can develop unusually large bones and other connective tissues.
Researchers who posted this early-stage study — not yet checked by independent experts — used mice carrying similar gene changes to study what goes wrong inside cells. They found that the faulty PDGFRb gene appears to switch on a growth signalling chain normally controlled by growth hormone, involving proteins called STAT5 and IGF1. Understanding this chain may, in future, help scientists develop treatments aimed at interrupting it.
This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
Read the original reporting — these are the public sources this summary draws from.
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-08-29Constitutive PDGFRb activation drives connective tissue overgrowth through STAT5-IGF1 signaling