The effect and mechanism of gene Fam20a on the development and function of salivary glands in mice

Abstract

Objective: The influence of the knockout of gene Fam20a on mice salivary glands was studied in this research, to provide a potential gene therapeutic target for salivary gland dysfunction.

Design: The control group with genotype Fam20a^f/f and conditional knockout (cKO) group with Fam20a^f/f;K14-Cre were constructed with Cre-Loxp. The influence of Fam20a on the salivary glands was studied in terms of morphology, functionality and molecular mechanism.

Results: In terms of morphology, the cross-sectional area ratio of ductal to the total was reduced in the cKO mice, while that of extracellular matrix to the total was increased. At the sub-microscopic level, the knockout of Fam20a led to abnormal sub-microscopic structure of the duct cells. Functionally, saliva flow rate was significantly reduced in cKO mice. The result was consistent with the change of acinar cell marker Aquaporin 5 which was abnormally diffusely expressed in the cytoplasm of acinar cells. Meanwhile, the expression of ductal cell markers Cytokeratin 7 and nerve growth factor β were significantly decreased, suggesting the abnormal development and function of the duct cells. The research on the mechanism reveals that the loss of Fam20a led to the decreased expression and varied localization of bone morphogenetic protein 4 (BMP4), and a significant decrease of the proportion of phosphorylated extracellular signal-regulated protein1/2 (ERK1/2) to total ERK1/2. These changes suggested that the loss of Fam20a attenuated the activity of the BMP/ERK signaling pathway.

Conclusions: Fam20a affects the morphology and function of salivary glands, probably by attenuating the activity of the BMP/ERK signaling pathway.

Keywords: BMP/ERK signaling pathway; FAM20A; Salivary gland.