# Development and characterization of an inducible Tensin1 deficient transgenic murine model

## TL;DR

This study creates a new mouse model to study Tensin1 and finds changes in gene expression and immune cell behavior when Tensin1 is removed.

## Contribution

A novel inducible TNS1-deficient transgenic mouse model was developed for lineage-specific and temporally controlled knockout.

## Key findings

- TNS1 knockout had no effect on mouse health, breeding, or organ histopathology.
- RNA sequencing revealed 171 differentially expressed genes linked to immune and osteoclast pathways.
- Loss of TNS1 impaired migration and phagocytosis in THP-1 cells and increased lymphocyte detection in bronchoalveolar lavage.

## Abstract

Tensin1 (TNS1) is a key component of focal and fibrillar adhesions, mediating fibrillogenesis, as well as the transduction of mechanical cues and adhesive signaling. To enable further TNS1 characterization, we have developed a novel transgenic mouse that allows for temporally controlled and lineage specific knockout of TNS1. We found no differentially observed effects of TNS1 knockout on mouse health, breeding capacity, or vital organ histopathology. In contrast, RNA sequencing analysis identified 171 differentially expressed genes with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrating differential expression in osteoclast differentiation and a number of pathways involved in host immune response. Furthermore, STRING pathway analysis showed differential regulation of genes involved in B-cell and myeloid-related signaling pathways, a number of which were validated by reverse transcription-quantitative polymerase chain reaction (RT qPCR). Loss of TNS1 in THP-1 monocyte/macrophage cell line resulted in impaired migration and phagocytosis. We also observed a trend toward increased detection of lymphocytes in the bronchoalveolar lavage within days following TNS1 knockout. This study provides a novel understanding of the phenotypic and genotypic changes that occur following knockout of TNS1 that may lead to subsequent understanding of its role in disease.

The online version contains supplementary material available at 10.1038/s41598-026-41319-3.