Ltbp1-flox Mouse

LTBP1, the latent transforming growth factor β binding protein 1, is a large extracellular matrix protein. It is an associated ligand of fibrillin-microfibrils and is well-known for its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, regulating their bioavailability. This function is crucial for maintaining the homeostasis of connective tissues [1].

In in vitro studies, LTBP1 coordinates the incorporation of fibrillin-1 and-2 into the extracellular matrix, and this function is differentially exerted by its short and long isoforms, uncovering a TGFβ-independent role potentially related to connective tissue disorders [1]. In human patients, bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome, with affected individuals showing connective tissue features, craniofacial dysmorphology, heart defects, and skeletal features. In vitro studies on proband-derived dermal fibroblasts and in vivo validation in zebrafish carrying ltbp1 mutations indicate that LTBP1 function is crucial for skin and bone ECM assembly and homeostasis [3]. In esophageal squamous cell carcinoma (ESCC), down-regulation of LTBP1 inhibits the invasion, migration, and metastatic abilities of cancer cells, and also reduces mesenchymal phenotypes and inhibits TGFβ-induced epithelial-mesenchymal transition (EMT). It also enhances ESCC cells' sensitivity to 5-FU treatment and attenuates cancer-associated fibroblasts (CAFs) transformation, suggesting an oncogenic role of LTBP1 in ESCC progression [2].

In conclusion, LTBP1 plays essential roles in extracellular matrix formation and connective tissue homeostasis. Its functions in diseases like cutis laxa syndrome and ESCC have been revealed through in vitro and in vivo studies including those using zebrafish models. Understanding LTBP1's functions can potentially provide new insights for treating connective tissue-related disorders and certain cancers.