Morphological and Functional Alterations of Ear in Lysosomal Protective Protein/Cathepsin A Gene Knock Out Mouse
- VernacularTitle:溶酶体保护蛋白/组织蛋白酶A基因敲除小鼠听力和耳形态学初步研究
- Author:
Yunkai GUO
;
Dinghua XIE
;
Xinming YANG
- Publication Type:Journal Article
- Keywords:
Lysosome;
Protective protein/cathepsin A(PPCA);
Knock out;
Galactosialidosis(GS);
Lysosomal storage disease;
Mouse
- From:
Journal of Audiology and Speech Pathology
1998;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective Galactosialidosis(GS) is an autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal ?-galactosidase and neuraminidase as a result of a primary defect in the protective protein/cathepsin A(PPCA).Mouse model of GS has been generated by targeted deletion of PPCA gene and closely resembled the phenotypes in human conditions.However,it remains to be determined whether hearing loss observed in human also occurs in the mouse model.In this study,we observed their alterations of the auditory function and morphology of the ear,and explored pathophysiological mechanisms of hearing impairment.Methods PPCA homozygous(PPCA-/-) mice at 1 and 2 months of age,and their wildtype littermates(PPCA+/+) were examined for auditory thresholds through auditory brainstem responses(ABR) to click,tone pips 8,16,and 32 kHz stimuli.Morphological analyses in ears were performed by series temporal bone section and light microscopy.Results PPCA-/-mice at 1 month of age showed a normal threshold and the morphology of ears.Up to 2months of age,their thresholds were elevated 40～45 dB SPL above those of PPCA+/+ mice.There were distinct pathological changes of middle and inner ear in PPCA-/-mice of 2 months old.The severe otitis media and the vacuolation associated with lysosomal storage were observed within ossicles and cochlear bone cells,stria vascularis cells,spiral ganglion neurons,spiral limbus,Reissner's membrane cells,and the mesothelial cells of the perilymphatic scala and basilar membrane,but not within the organ of Corti.Vestibular organ did not show vacuolation.Conclusion The deficiency of lysosomal protective protein/cathepsin A may result in hearing loss and morphological alterations of ear.The otitis media and ossicle changes,and the defects in lysosomal storage of neurons,stria vascularis,spiral limbus,Reissner's membrane and basilar membrane cells may contribute to the conductive and sensorineural hearing loss respectively.
