Generation of a Mouse Model Recapitulating Skeletal Abnormalities of Trichorhinophalangeal Syndrome (TRPS)

Naoya SAEKI, Makoto ABE, Shinsuke OHBA,
Department of Tissue and Developmental Biology

The research group has generated a mouse model that recapitulates postnatal skeletal abnormalities observed in patients with Trichorhinophalangeal syndrome (TRPS). TRPS is a genetic disorder caused by point mutations or deletions in the transcription factor TRPS1. TRPS patients display a range of skeletal dysplasia, including reduced jaw size, short stature, and a cone-shaped digit epiphysis. Some TRPS patients experience an early onset of coxarthrosis, which severely affects their daily activities. Pathological mechanisms underlying TRPS have been analyzed using Trps1 knockout mice. However, the mice die shortly after birth, which makes it difficult to analyze the skeletal abnormalities that postnatally develop in TRPS patients. In this study, they identified candidate enhancer regions, which regulate the expression of the Trps1 gene, through next-generation sequencer-based analysis and generated enhancer knockout (KO) mice by deleting the genomic regions. The enhancer KO mice survived postnatally and were fertile. Expression of the Trps1 gene was downregulated in various tissues in these mice. They exhibited growth impairments and morphological abnormalities in the hip joint, recapitulating postnatal features observed in TRPS patients. Thus, the mouse model will contribute to the understanding of postnatal TRPS pathologies, especially growth impairments and skeletal abnormalities, which have been challenging to study in model animals. A series of the studies will lead to the development of novel therapeutic strategies for TRPS.

This article, “Deletion of Trps1 regulatory elements recapitulates postnatal hip joint abnormalities and growth retardation of Trichorhinophalangeal syndrome in mice” was published in Human Molecular Genetics at DOI: https://doi.org/10.1093/hmg/ddae102