Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia.

A J May,G B Proctor,L Chatzeli,A S Tucker

doi:10.2174/1566524015666150831141307

Abstract

Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia.

Highlights

Mice and humans have three pairs of major salivary glands that secrete into the oral cavity: the parotid (PG), submandibular (SMG) and sublingual glands (SLG), as well as numerous minor salivary glands which are located in the tongue, palate, cheeks and lips [1]
A reduction in saliva leads to xerostomia, or dry mouth, an oral symptom that can seriously impinge on the quality of life in human patients
No obvious difference in histology was evident between Fgf10 WT and +/- littermates at P14 (Fig. 1)

Summary

Introduction

Mice and humans have three pairs of major salivary glands that secrete into the oral cavity: the parotid (PG), submandibular (SMG) and sublingual glands (SLG), as well as numerous minor salivary glands which are located in the tongue, palate, cheeks and lips [1]. The major salivary glands are derived from the oral ectoderm and neural crest derived mesenchyme [2, 3] The saliva they produce is essential for the well being of the oral cavity, producing lubricants, digestive enzymes, anti-microbials, and buffering the pH of the mouth [4]. A reduction in saliva leads to xerostomia, or dry mouth, an oral symptom that can seriously impinge on the quality of life in human patients. This hyposalivation leads to problems such as mastication difficulties, halitosis, deficiency of taste and a high incidence of caries and candida infections. Patients exposed to radiation therapy for the treatment of head and neck cancers develop xerostomia due to severe damage of the salivary

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Conclusion