Evidence for Heterozygous Abnormalities of the Elastin Gene (ELN) Affecting the Quantity of Vocal Fold Elastic Fibers: A Pilot Study

Objectives To investigate the effects of a heterozygous elastin gene (Eln) abnormality (deletion of one Eln allele) on the structural characteristics of the vocal fold lamina propria using a mouse model of human disease. Study Design Cross-sectional between-subjects design. Methods Five mice, four with heterozygous Eln deletions (Eln +/−) serving as an animal model for the human disease supravalvular aortic stenosis and one normal wild-type control (Eln +/+) were used for this study. Vocal folds were obtained from each animal and stained for the protein elastin using histochemical methods. Descriptive data from qualitative visual inspection and quantitative data from microscopic digital image analysis were collected to determine the staining density of elastic fibers within the vocal fold lamina propria. Results Qualitative visual inspection revealed greater staining density (eg, a greater quantity) for elastic fibers in the Eln +/+ animal. Quantitative measurements using digital pixel analysis of staining density revealed significant differences between mice with the two genotypes, confirming the qualitative findings. Conclusions Results suggest that Eln requires two functioning alleles for normal structural development of the vocal fold lamina propria. This pilot evidence supports the hypothesis of a structural etiology causing altered vocal function in humans with a similar genotype.