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

View Article: PubMed Central

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.

No MeSH data available.


Comparison of WT and Fgf10 +/- salivary glands at P14. General duct and acini arrangements of WT and Fgf10 +/- SMG and SLGs appeared normal at P14 (A-D). A reduction in size was seen in glandular lobes in Fgf10 +/- animal compared to WT littermates (black dotted line) (A, B). At E18.5 no apparent histological differences were observed in WT and Fgf10 +/- littermates (E, F). At P14 combined Fgf10 +/- SMGs and SLGs weighed significantly less compared to WT littermates (G). P14; scale bar = 200I1/4M. A-D shows glands from female specimens. E, F shows E18.5 glands; SMG (black line), SLG (red line), scale bar = 200I1/4M. (Color images available online).
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Figure 1: Comparison of WT and Fgf10 +/- salivary glands at P14. General duct and acini arrangements of WT and Fgf10 +/- SMG and SLGs appeared normal at P14 (A-D). A reduction in size was seen in glandular lobes in Fgf10 +/- animal compared to WT littermates (black dotted line) (A, B). At E18.5 no apparent histological differences were observed in WT and Fgf10 +/- littermates (E, F). At P14 combined Fgf10 +/- SMGs and SLGs weighed significantly less compared to WT littermates (G). P14; scale bar = 200I1/4M. A-D shows glands from female specimens. E, F shows E18.5 glands; SMG (black line), SLG (red line), scale bar = 200I1/4M. (Color images available online).


Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia
Comparison of WT and Fgf10 +/- salivary glands at P14. General duct and acini arrangements of WT and Fgf10 +/- SMG and SLGs appeared normal at P14 (A-D). A reduction in size was seen in glandular lobes in Fgf10 +/- animal compared to WT littermates (black dotted line) (A, B). At E18.5 no apparent histological differences were observed in WT and Fgf10 +/- littermates (E, F). At P14 combined Fgf10 +/- SMGs and SLGs weighed significantly less compared to WT littermates (G). P14; scale bar = 200I1/4M. A-D shows glands from female specimens. E, F shows E18.5 glands; SMG (black line), SLG (red line), scale bar = 200I1/4M. (Color images available online).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998116&req=5

Figure 1: Comparison of WT and Fgf10 +/- salivary glands at P14. General duct and acini arrangements of WT and Fgf10 +/- SMG and SLGs appeared normal at P14 (A-D). A reduction in size was seen in glandular lobes in Fgf10 +/- animal compared to WT littermates (black dotted line) (A, B). At E18.5 no apparent histological differences were observed in WT and Fgf10 +/- littermates (E, F). At P14 combined Fgf10 +/- SMGs and SLGs weighed significantly less compared to WT littermates (G). P14; scale bar = 200I1/4M. A-D shows glands from female specimens. E, F shows E18.5 glands; SMG (black line), SLG (red line), scale bar = 200I1/4M. (Color images available online).

View Article: PubMed Central

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.

No MeSH data available.