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K P Steel

Publications and source records attributed to K P Steel.

18 recordsLinked to original sources
PubMed1992

A histologic study of nonmorphogenetic forms of hereditary hearing impairment.

It appears that many forms of syndromic and nonsyndromic hereditary hearing impairment are secondary to either neuroepithelial or cochleosaccular dysfunction. Making this distinction can be difficult in human temporal bone specimens; however, this added knowledge may ultimately provide prognostic and therapeutic information in hearing habilitation. Fundamental studies using animal models of different types of hereditary deafness may also prove useful in this respect.

Adult↗
PubMed1992

The development and interpretation of the summating potential response.

The development of cochlear responses in the mouse was investigated, recording from the round window. Positive summating potentials (SP) could be detected as early as 7 days after birth in some individuals, the first signs of negative SP occurred in mice aged 10 days, and compound action potentials were first detected at 11 days of age. These early responses were obtained with relatively low frequency stimuli (usually 6 kHz). All waveforms recorded from 20 day old mice could be interpreted as simple additions of positive and negative SP and compound action potentials, each with different amplitudes and latencies. Positive SP showed both fast and slow components. Our observations are consistent with the positive SP with only a fast component arising from the basal turn inner hair cells, the positive SP with fast and slow components being generated by both inner and outer hair cells in the basal turn, and the negative SP seen at low frequencies of stimulation originating from depolarisation of hair cells in the apical turn. Summating potentials may thus be useful for investigating inner and outer hair cell function separately in abnormal cochleas in which it is not known which cell type primarily is affected.

Acoustic Stimulation↗
PubMed1992

Characteristics of stria vascularis melanocytes of viable dominant spotting (Wv/Wv) mouse mutants.

The Wv mutation lies in the kinase domain of the proto-oncogene c-kit which is expressed in a variety of cells including neural crest derived melanoblasts. The mutation results in the abnormal migration, proliferation, survival and/or differentiation of melanoblasts. Viable Dominant Spotting (Wv/Wv) mouse mutants have a white coat due to the absence of melanocytes. The majority of these animals have no melanocytes within the stria vascularis and no endocochlear potential (EP). A proportion of homozygous mutants partially escape the effects of the mutation: 47.2% of pinnae and 21% of vestibular regions were pigmented and 10.8% of ears had an EP. All ears with an EP that were available for histology had some pigmentation of the stria. There was no obvious correlation between external and internal spotting in Wv/Wv mice, and asymmetrical pigmentation of the ears was common. Both light and dark intermediate cells (which are derived from melanocytes) were present in the middle and/or basal turns of these cochlear ducts and they appeared to function normally in enabling the stria to produce an EP (although the EP was usually lower than normal). This suggests that the c-kit gene product is needed only during development of the stria, and not for mature melanocyte function because the melanocytes present in the mutant strias were carrying the mutant version of the c-kit gene. Melanocytes were similar in appearance in controls and mutants, except that fewer melanin granules were observed in the strias of Wv/Wv mice. The observations that strial melanocytes with very few melanin granules in Wv/Wv mutants are able to support EP production, together with previous observations that albino animals with strial melanocytes but no melanin have a normal EP, suggest that melanocytes but not melanin are essential for normal strial function.

Animals↗
PubMed1992

Close linkage of the olfactory marker protein gene to the mouse deafness mutation shaker-1.

One thousand sixty-six progeny have been generated from a backcross segregating for the mouse deafness mutation, shaker-1 (sh-1). One thousand fifty-two mice were analyzed for a protein polymorphism segregating for the distal flanking marker, beta-globin (Hbb), and 13 recombinants between Hbb and sh-1 were identified. One thousand eight mice were analyzed for a restriction fragment length polymorphism segregating for the proximal flanking marker, tyrosinase (c), and 54 recombinants between c and sh-1 were identified, completing a panel of 67 recombinant mice from the backcross in the vicinity of the sh-1 mutation. This panel allows the identification of markers closely linked to the sh-1 mutation that may act as start points for a chromosomal walk to the gene. One such marker, the olfactory marker protein gene (Omp), is recombinant with sh-1 in only one mouse from the recombinant panel. Thus, the Omp gene lies 0.1 cM from sh-1, on average, a distance of 200 kb. Haplotype analysis indicates that Omp lies proximal to sh-1.

Animals↗
PubMed1992

Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1.

Splotch is considered a model of Waardenburg syndrome type I (WSI) because the abnormalities are caused by mutations in homologous genes, Pax-3 in mice and PAX3 (HuP2) in humans. We examined inner ear structure and function in Splotch mutants (Sp/+) and found no sign of auditory defects, in contrast to the deafness in many WSI individuals. The difference in expression of the genes in the two species may be due to different parts of the gene being mutated, or may result from variations in modifying influences as yet undefined.

Animals↗
PubMed1992

TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor.

We have used a probe derived from TRP-2/DT to detect migratory melanoblasts shortly after they emerge from the neural crest, as early as 10 days post coitum (dpc). TRP-2/DT expression is otherwise restricted to the presumptive pigmented retinal epithelium, the developing telencephalon and the endolymphatic duct. The pattern of steel and c-kit hybridisation in the developing brain differed from that of TRP-2. TRP-1 and tyrosinase probes also detected melanoblasts but were both expressed later in development than TRP-2. We used the TRP-2/DT probe to investigate the way that the Steel-dickie (Sld) mutation interferes with melanocyte development, and found that the membrane-bound steel growth factor which is missing in Sld/Sld mutants is necessary for the survival of melanoblasts but not for their early migration and initial differentiation.

Animals↗
PubMed1991

Identification of two types of melanocyte within the stria vascularis of the mouse inner ear.

We have distinguished two types of melanocyte within the intermediate layer of the stria vascularis in the cochlea of normally pigmented mice: light and dark intermediate cells. The light intermediate cells are present in the stria from birth and have the typical appearance of a melanocyte. They are large and dendritic with electron-lucent cytoplasm containing numerous vesicles that show tyrosinase activity, and pigment granules in various stages of development. These granules have the ultrastructural and histochemical characteristics of premelanosomes and melanosomes. The light intermediate cells persist throughout life, but less frequently contain pigment in older animals. The dark intermediate cells, present only in adult mice, vary considerably in number and distribution between animals. Pigment granules, bound within an electron-dense acid phosphatase-rich matrix, form the main component of the dark intermediate cells. The intermediate cells may comprise either two distinct cell populations or different developmental stages of the same cell type; ultrastructural observations suggest the latter. In young mice, light intermediate cells contain the electron-dense matrices, which at later stages of development are found almost exclusively in dark cells. The dark intermediate cells contain few cell organelles other than pigment granules accumulated within lysosomal bodies and they often have pycnotic nuclei. These observations suggest that the dark intermediate cells are a degenerate form of the light intermediate cells. Clusters of melanosomes also occur in the basal cells, and to a much lesser extent in the marginal cells. These cells do not stain after incubation in DOPA, suggesting that they are not capable of melanin synthesis, and therefore probably acquire melanin by donation from adjacent melanocytes. Pigment clusters are also found within the spiral ligament at all stages of development.

Age Factors↗
PubMed1989

Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggests no spontaneous activity of cochlear origin.

Deafness mutant mice show no stimulus-related cochlear potentials as well as abnormal electrically-evoked responses recorded from the inferior colliculus. Abnormal spontaneous activity in the auditory periphery could result in abnormal development and/or maintenance of the central auditory pathways. We therefore assessed spontaneous activity of cochlear origin in the central nuclei of the mutants by ablating one cochlea and subsequently using the 2-deoxyglucose (2DG) technique to study metabolic activity. Any asymmetries in labeling in a given nucleus should be due to spontaneous activity in the cochlear nerve on the unoperated side. In control animals (+/dn mice undergoing unilateral cochlea ablation), statistically significant decreased 2DG labeling was observed in the ipsilateral PVCN and AVCN, and contralateral MNTB and IC; all receive primary excitatory input from the ablated ear. No significant differences in labeling between right and left sides were observed in any of the nuclei studied in the mutant animals. These findings suggest that there is no spontaneous activity of cochlear origin in these mutants, even though many cochlear nerve fibers and spiral ganglion cells survive.

Animals↗
PubMed1989

Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear.

The stria vascularis of the mammalian cochlea is composed primarily of three types of cells. Marginal cells line the lumen of the cochlear duct and are of epithelial origin. Basal cells also form a continuous layer and they may be mesodermal or derived from the neural crest. Intermediate cells are melanocyte-like cells, presumably derived from the neural crest, and are scattered between the marginal and basal cell layers. The marginal cells form extensive interdigitations with the basal and intermediate cells in the normal adult stria. The stria also contains a rich supply of blood vessels. We investigated the role of melanocytes in the stria vascularis by studying its development in a mouse mutant, viable dominant spotting, which is known to have a primary neural crest defect leading to an absence of recognisable melanocytes in the skin. Melanocytes were not found in the stria of most of the mutants examined, and from about 6 days of age onwards a reduced amount of interdigitation amongst the cells of the stria was observed. These ultrastructural anomalies were associated with strial dysfunction. In the normal adult mammal, the stria produces an endocochlear potential (EP), a resting dc potential in the endolymph in the cochlear duct, which in mice is normally about +100 mV. In our control mice, EP rose to adult levels between 6 and 16 days after birth. In most of the mutants we studied, EP was close to zero at all ages from 6 to 20 days. Melanocyte-like cells appear to be vital for normal stria vascularis development and function. They may be necessary to facilitate the normal process of interdigitation between marginal and basal cell processes at a particular stage during development, and the lack of adequate interdigitation in the mutants may be the cause of their strial dysfunction. Alternatively, melanocytes may have some direct, essential role in the production of an EP by the stria. Melanocytes may be important both for normal strial development and for the production of the EP. We believe this is the clearest demonstration yet of a role for migratory melanocytes other than their role in pigmentation.

Animals↗
PubMed1987

Strial dysfunction in mice with cochleo-saccular abnormalities.

Most viable dominant spotting (Wv/Wv) mutant mice, which show cochleo-saccular degeneration, were found to have an endocochlear potential (EP) around zero together with a structurally abnormal stria vascularis. Inner hair cells were well preserved, but outer hair cells in the basal half of the cochlea were degenerating, possibly as a result of primary strial dysfunction. Thresholds for the detection of a compound action potential were raised to around 100 dB SPL in the mutants with no EP, and there was little if any cochlear microphonic at the round window. Of the 20 Wv/Wv mice studied, five partially escaped the effects of the mutation and had measurable positive potentials (15-86 mV) in scala media in the basal turn; responses in these animals were intermediate between control responses and those of mutants with no EP. These findings confirm that the pathological processes in this mutant, with cochleo-saccular abnormalities, are fundamentally different from the pathological processes in animals with neuroepithelial abnormalities reported previously [see Steel and Bock (1983) Arch. Otolaryngol. 109, 22-29, for references].

Animals↗
PubMed1987

Mixed conductive and sensorineural hearing loss in LP/J mice.

Air and bone conduction thresholds for the detection of a compound action potential response were measured in mice of the LP/J inbred strain, which has been proposed as a possible model for human otosclerosis. Thresholds were compared with control data from CBA/Ca mice. Evidence of a mixed sensorineural and conductive hearing loss was obtained in LP/J mice. Few signs of hair cell degeneration or middle-ear bony lesions were found in 20-day old mice, although they generally showed raised thresholds to both air and bone conducted stimuli. The reason for the observed sensorineural component of the hearing loss at this age is not clear, since endocochlear potentials were normal in mice of this strain. By 225 days of age, hair cell loss was extensive and there was clearly excess bone growth in all middle-ear specimens studied, particularly on the incus and the cochlear wall facing the middle ear. Microbiological analysis of LP/J specimens revealed no evidence of a middle-ear infection specific to these mice which might explain the pathology.

Action Potentials↗
PubMed1987

Glycoconjugates of the tectorial membrane.

The type and quantity of carbohydrate present in the tectorial membrane (TM) was analysed using gas-liquid chromatography and lectin staining of TM protein subunits previously separated by electrophoresis. A relatively large amount of carbohydrate was found, and glucose, N-acetylglucosamine, N-acetylgalactosamine, galactose, mannose and N-acetylneuraminic acid were detected. The presence of mannose and the reaction of many of the protein bands with lectins suggest that at least part of the carbohydrate present is in the form of glycoprotein. The reaction of the main protein band with the lectins RCA1 and ConA is consistent with the suggestion [Thalmann et al. (1985) J. Acoust. Soc. Am. Suppl. 1, Vol. 78, S66] that this band is similar to collagen type II. The failure to detect any uronic acid in these experiments indicates that the more common proteoglycans are probably not a major component of the TM (although keratan sulphate might be present).

Animals↗
PubMed1987

The endolymphatic sac in a mouse mutant with cochleo-saccular degeneration. Electrophysiological and ultrastructural correlations.

The response of the endolymphatic sac to a disturbance in endolymph homeostasis was investigated by examining the sac in a mouse mutant, viable dominant spotting, which is known to exhibit primary strial dysfunction and cochleo-saccular degeneration. The function of the vascular stria was assessed by measuring the endocochlear potential and the sacs were then studied by light and transmission electron microscopy. The endolymphatic sac was found to be morphologically abnormal in these mutants, the main abnormality being the presence of granular epithelial cells, which showed clear histological signs of secretory activity. A stainable precipitate, believed to be secreted by the granular cells, was observed in the lumen of the endolymphatic sac in the mutants. The findings strengthen the view that the sac is involved in the regulation of endolymph volume and pressure.

Animals↗
PubMed1985

Genetic factors affecting hearing development.

Both genetic background and single gene mutations may affect the development of the auditory system. A classification system is presented for those single gene mutations causing hearing impairment. The new feature of this classification is the inclusion of a category for hereditary deafness of central origin. The other categories involve peripheral abnormalities and are: morphogenetic defects, in which the overall structure of the labyrinth is deformed; neuroepithelial degeneration, in which the primary defect appears to occur in the organ of Corti; and cochleo-saccular degeneration, where the stria vascularis is abnormal and Reissner's membrane collapses, leading to further degeneration.

Animals↗
PubMed1985

Electrical stimulation of the auditory system in animals profoundly deaf from birth.

Animals homozygous for the recessive deafness gene (dn/dn) have been used to study central responses to modiolar or round window electrical stimulation. Inferior colliculus evoked responses to contralateral constant current pulses are larger in mutants than in controls. In mutants, responses are largest in animals aged 5-7 months, compared with animals aged 42-50 days or 13.5-19 months. The spiral ganglion cell density is normal in the youngest group, but decreases significantly in older animals. Electrical stimulation of the round window is less effective than modiolar stimulation. Single unit recordings suggest that the larger evoked responses in deafness mice are produced by stronger discharges in neurones, rather than greater synchrony of discharge. The deafness mutation appears to provide a useful animal model for studying electrical stimulation of a central pathway which has never received stimulus-related input.

Age Factors↗