Barbara A. Bohne, Ph.D.
Gary W. Harding, M.S.E.
Dept. of Otolaryngology, Washington University School of Medicine, St. Louis, MO
Under Construction
Previous studies have reported that mice homozygous for the viable dominant spotting gene have impaired auditory function and lack a normal positive endocochlear potential (EP). We determined auditory sensitivity (e.g., compound APs) and EP level in the basal turn of controls (+/+), heterozygote and homozygote mice and correlated these data with the chemical composition of endolymph (measured with ion-sensitive electrodes) and the histological appearance of the stria vascularis. Endolymphatic [K+] (145mM) was near control values (169mM) in the homozygous mice whereas EP was reduced and both auditory potentials and [Ca++] were elevated. This finding indicates that the endolymph-perilymph barrier is intact and that K+ homeostasis must be near normal in the mutant. Endolymphatic potentials ranging from -0.3mV to +76mV were recorded in different animals. Those animals with a positive EP always had some melanocytes in their stria; higher EP values were associated with more strial melanocytes. Strial melanocytes were entirely missing in animals with a zero or slightly negative EPs. These findings suggest that endolymph K+ homeostasis and EP generation are accomplished by separate processes and possibly different cells within the stria vascularis.
Wheels (Whl), is a new semidominant complex neurological mutation. Behavioral anomalies in Whl mice include a prolonged circadian rhythm, bidirectional circling and abnormal responses to light. The inner ears of 13 mice carrying one copy of the mutant Whl gene (determined by DNA testing) were examined histologically. Variable pathological changes were found in individual animals which ranged from slight atrophy of the crista in one or more of the semicircular canals (in behaviorally normal animals) to complete absence of the lateral semicircular canal and crista (in some rapidly circling mice).
Mice homozygous for the tilted (tlt) gene may hold their head cocked to one side. When dropped into a tank of water, they sink to the bottom and do not resurface (termed swim-0), whereas wild-type mice promptly surface and swim to the side of the tank (termed swim-5). Some tilted mice exhibit intermediate swimming behavior in that they resurface but then swim in circles with their heads tilted to one side (termed swim-3). The inner ears of forty-seven 2-month-old mice (16 swim-0; 20 swim-3; 11 swim-5) were examined histologically. All swim-5 mice had a full complement of otoconia in the saccule and utricle in both inner ears. Many swim-3 mice had either 1-5 giant otoconia or a moderate number of moderate-sized otoconia in the saccule of one ear. All swim-0 mice lacked otoconia in the utricle and saccule while the sensory epithelium and the gelatinous component of the otolithic membrane were intact. Semi-thick and thin radial sections of utricular and saccular maculae from normal and tlt/tlt mice were examined by light and TEM, respectively. We looked for cytological differences between the sensory epithelium in these mice such as an accumulation of secretory granules in the supporting cells, or differences in the morphology of the otolithic membrane.
Mice which lack fibroblastic growth factor receptor 3 (FGFR3) have inner-ear defects. FGFR3 knockout mice have moderate to severe skeletal anomalies which worsen with age. The skeletal problems include retarded growth, tail kinks, kyphosis and hip dysplasia. The inner ears of one 2-wk-old, one 3-wk-old and one 6-wk-old FGFR3 knockout mice were examined histologically. The bony and membranous labyrinths were grossly normal. No defects were noted in the vestibular organs or endolymphatic duct/sac. The density of IHCs and OHCs per millimeter of the OC in the 6-wk-old FGFR3 knockout was 117 and 388, respectively, nearly identical to its normal littermate (IHCs - 117; OHCs - 381). Compared to normal mice (Fig. 4A), several defects were found in the cochlea including a lack of inner and outer pillars, lack of a tunnel space and greatly reduced innervation of the OHCs; the presence of extra cells between the hair cells and the BM, 2-3 extra rows of Deiters' cells, a prominent blood vessel below the BM and many mesothelial cells on the scala tympani (ST) side of the BM (Fig. 4B). The FGFR3 ears seemed to be much younger developmentally than the animal's chronological age (Kikuchi & Hilding, 1965; Kraus & Aulbach-Kraus, 1981), as if development had been arrested (Fig. 5).
Fig. 4 Thick radial sections of a normal mouse organ of Corti (A) and FGFR3
knockout (B).
Fig. 5 Diagram of the newborn mouse organ of Corti.
The hearing of five 3-wk-old FGFR3 knockout mice and their normal littermates was tested using a short whistle blast (2500-3150 Hz, 85-95 dB) immediately prior to sacrifice. All controls exhibited a normal Preyer reflex and startle response. Four of five knockout mice had no responses while the fifth knockout mouse responded very weakly. The cochleas of all mice were then prepared for histological examination. The cochleas from additional knockout mice were evaluated. Segments of OC from the apical and basal turns of several normal and knockout mice were sectioned for light and TEM study. Ultrastructural data collected include: the number, arrangement and ultrastructural appearance of the microtubules in the Deiters' and pillar cells; and the number and type(s) of nerve endings on the OHCs and IHCs.
Copyright © 1997, Barbara A. Bohne and Gary W. Harding
Last updated 4/20/97