Deafness in Australian Cattle Dogs associated to QTL on chromosome 20 in genome-wide association study analyses.

Pigment-associated deafness is a common hereditary condition in a range of dog breeds. The aim of this study was to perform a genome-wide association analysis to investigate the genetic architecture of deafness in Australian Cattle Dogs. Genotypes for 104 757 polymorphisms in 216 dogs were available for analyses after quality control. A genomic relationship matrix was used in the mixed model analyses to account for polygenic effects, as we tested each polymorphism for its association with deafness, in a case/control experimental design. Three approaches were used to code the genotypes and test for additive, recessive and dominant SNP effects. The genome-wide association study analyses identified a clear association peak on CFA20, with the most significant SNPs on this chromosome (1.29 × 10-4 ) in the vicinity of MITF. Variants in MITF have been associated with white pigmentation in dogs and with deafness in humans and other species, supporting the premise that canine deafness is associated with variants in or near this gene. A recessive inheritance for the peak in CFA20 is possible given the significant results in the recessive model; however, the estimated heritability was low (4.54 × 10-5 ). Further validation, identification of variants and testing in other dog breeds are needed.

Distortion product otoacoustic emissions in geriatric dogs.

Recordings of distortion product otoacoustic emissions (DPOAE) were taken from 28 geriatric dogs aged 12.2 ± 2.2 years and 15 control dogs aged 5.9 ± 3.0 years (mean ± standard deviation) to demonstrate frequency-specific changes in cochlear responses. Recordings were performed for primary frequencies of 2-12 kHz in 2 kHz increments. Brainstem auditory evoked response (BAER) recordings were also made from geriatric dogs for comparison with DPOAE responses. Significant decreases in DPOAE response amplitudes were observed at frequencies of 6-12 kHz in geriatric dogs compared to control dogs, reflecting loss of cochlear outer hair cells along the length of the cochlea. Significant decreases in response amplitudes were not seen at frequencies of 2 or 4 kHz. Decreases in BAER response amplitudes subjectively paralleled the depressed DPOAE amplitudes. No significant linear regression relationships were found for DPOAE response amplitude vs. age despite the progressive nature of age-related hearing loss. The reductions in response at all frequencies starting at the age where dogs are considered geriatric indicate that age-related hearing loss begins earlier in the life span. DPOAE recordings provide a means to assess cochlear function across different portions of the auditory spectrum for assessing hearing loss associated with aging, and potentially for losses from other causes of decreased auditory function.

Congenital deafness in Jack Russell terriers: prevalence and association with phenotype.

Congenital hereditary sensorineural deafness is the most common form of deafness in dogs. The objectives of this study were to determine a reliable measure of the prevalence of deafness in Jack Russell terriers, an affected breed, and associations between deafness and phenotypic characteristics. Brainstem auditory evoked response recordings and phenotypic parameters (coat color, coat texture, sex, eye color, sire and dam hearing status) were recorded for 1009 Jack Russell terriers. The prevalence of unilateral and bilateral deafness was 3.57% and 0.50%, respectively, lower by a factor of three to four than in earlier reports based on smaller and closely related kindreds. Significant association with deafness was identified with white coat color and parental hearing status, but not with sex or coat type. Lack of significant sex or coat type associations and the significant association with white coat color are consistent with previous reports. In conclusion the prevalence of deafness in Jack Russell terriers is lower than initially reported. Deafness was associated with white coat color and parental hearing status. The association with parental hearing status supports this form of deafness being a heritable trait in the breed and the association with white coat color supports an inheritance linked to pigmentation genes.

Prevalence of deafness in dogs heterozygous or homozygous for the merle allele.

BACKGROUND: Deafness in dogs is frequently associated with the pigment genes piebald and merle. Little is known about the prevalence of deafness in dogs carrying the merle allele. OBJECTIVE: To determine the prevalence of deafness in dogs heterozygous and homozygous for the merle allele of the mouse Silver pigment locus homolog (SILV) gene. ANIMALS: One hundred and fifty-three privately owned merle dogs of different breeds and both sexes. METHODS: Hearing was tested by brainstem auditory-evoked response and classified as bilaterally hearing, unilaterally deaf, or bilaterally deaf. DNA from buccal cells was genotyped as either heterozygous or homozygous for the merle allele. Deafness association tests among merle genotype, eye color, and sex were performed by the chi(2) test. RESULTS: Deafness prevalence in merles overall was 4.6% unilaterally deaf and 4.6% bilaterally deaf. There was a significant association between hearing status and heterozygous versus homozygous merle genotype. For single merles (Mm), 2.7% were unilaterally deaf and 0.9% were bilaterally deaf. For double merles (MM), 10% were unilaterally deaf and 15% were bilaterally deaf. There was no significant association with eye color or sex. CONCLUSIONS: Deafness prevalence in merle dogs was greater than that in some dog breeds homozygous for the piebald gene, such as the English Cocker Spaniel, but comparable to, or lower than, that in the Dalmatian and white Bull Terrier. Dogs homozygous for the merle allele were significantly more likely to be deaf than heterozygotes.

Heritability and segregation analysis of deafness in U.S. Dalmatians.

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Effect of hyperbaric oxygen treatment on incorporation of an autogenous cancellous bone graft in a nonunion diaphyseal ulnar defect in cats.

OBJECTIVE: To determine whether hyperbaric oxygen treatment (HBOT) would affect incorporation of an autogenous cancellous bone graft in diaphyseal ulnar defects in cats. ANIMALS: 12 mature cats. PROCEDURE: Bilateral nonunion diaphyseal ulnar defects were created in each cat. An autogenous cancellous bone graft was implanted in 1 ulnar defect in each cat, with the contralateral ulnar defect serving as a nongrafted specimen. Six cats were treated by use of hyperbaric oxygen at 2 atmospheres absolute for 90 minutes once daily for 14 days, and 6 cats were not treated (control group). Bone labeling was performed, using fluorochrome markers. Cats were euthanatized 5 weeks after implanting, and barium sulfate was infused to evaluate vascularization of grafts. Ulnas were evaluated by use of radiography, microangiography, histologic examination, and histomorphometric examination. RESULTS: Radiographic scores did not differ between treatment groups. Microangiographic appearance of grafted defects was similar between groups, with all having adequate vascularization. Differences were not observed between treated and nontreated groups in the overall histologic appearance of decalcified samples of tissue in grafted defects. Mean distance between fluorescent labels was significantly greater in cats given HBOT than in nontreated cats. Median percentage of bone formation in grafted defects was significantly greater in cats given HBOT. CONCLUSIONS: Hyperbaric oxygen treatment increased the distance between fluorescent labels and percentage of bone formation when incorporating autogenous cancellous bone grafts in induced nonunion diaphyseal ulnar defects in cats, but HBOT did not affect revascularization, radiographic appearance, or qualitative histologic appearance of the grafts.

Congenital deafness and its recognition.

Congenital deafness in dogs and cats is primarily of the hereditary sensorineural form associated with white pigmentation genes, although acquired forms of deafness are possible. Highest prevalence is seen in white cats, especially those with blue eyes, and the Dalmatian, with many other dog breeds affected to some extent. This deafness results from degeneration of the cochlear blood supply at age 3-4 weeks, presumably resulting from suppression of melanocytes by the white (cat) or merle or piebald (dog) genes. Mechanism of inheritance is not understood for most breeds. Such animals should not be bred and may present liabilities for their owners. Objective diagnosis of deafness, especially when unilateral, relies on the brainstem auditory evoked response, an electrodiagnostic test where electrical activity in response to a click stimulus is recorded from the scalp using needle electrodes and a special purpose computer. Client counseling guidelines are presented.

Effect of hyperbaric oxygen on lipid peroxidation in free skin grafts in rats.

OBJECTIVE: To document that free skin grafts treated with hyperbaric oxygen (HBO) are at greater risk for reperfusion injury, resulting in lipid peroxidation, than are free skin grafts without HBO treatment. ANIMALS: 40 Sprague-Dawley rats. PROCEDURE: Free skin grafting was performed bilaterally on each rat. The HBO-treated rats received HBO twice daily for 90 minutes at 2 ATA. Biopsy specimens were taken from each rat at the time of grafting and on days 2, 4, 7, 10, 14, 21, and 28, then were processed for tissue concentration of total glutathione (GSHt), glutathione peroxidase activity (GPx), and presence of thiobarbituric acid-reactive substances (TBARS). RESULTS: Both groups had a similar pattern of change in TBARS and GPx values--initial increase, returning to preoperative values at days 21 (control) and 28 (HBO). The GPx activity peaked later than did TBARS concentration (day 7 vs day 4). The pattern was significantly more pronounced in HBO-treated than in control rats. Both groups had a similar pattern of change in GSHt values-significant decrease from preoperative concentration at day 2, return to preoperative concentration by days 4 (HBO) and 7 (control), increase above preoperative concentration by day 21, and return to preoperative concentration by day 28. Obvious visual or histologic differences in the grafts were not detected between groups. CONCLUSIONS: Cellular effects of oxidative stress were apparent in both groups of rats; however, the degree of these effects was exacerbated by HBO. In the face of enhanced cellular lipid peroxidation, use of HBO for the treatment of free skin grafts must be questioned.

Autonomic regulation of gastric ulcerogenesis after cervical cord transection in the rat.

OBJECTIVE: To examine the role of anticholinergic and sympathomimetic drugs in preventing gastric ulcerogenesis after cervical cord transection (CCT) in the rat. METHODS: A randomized, prospective, interventional trial was performed comparing pirenzepine (muscarinic type I receptor antagonist) and ephedrine (nonspecific sympathomimetic) in the prevention of gastric ulcerogenesis after CCT in the rat. After isoflurane-induced general anesthesia, group 1 (n = 12) received sham CCT with no pretreatment, group 2 received CCT with no pretreatment, group 3 received CCT with pirenzepine pretreatment (0.01/mg/kg IP), and group 4 received CCT with ephedrine pretreatment (3 mg/kg IP). Six hours after intervention, all the rats were euthanized with isoflurane, stomachs were dissected, and a gastric ulcer index was determined. RESULTS: The mean (+/- SD) ulcer index was 0.08 +/- 0.1 for group 1, 2.33 +/- 0.5 for group 2 (p = 0.01), 0.41 +/- 0.7 for group 3 (p = 0.037 compared with group 2), and 0.75 +/- 0.7 for group 4 (p = 0.0005 compared with group 2). Groups 3 and 4 were not significantly different from each other (p = 0.30). CONCLUSIONS: Gastric ulcerogenesis after CCT in the rat is decreased by anticholinergic and sympathomimetic drug pretreatment.

Air- and bone-conduction brainstem auditory evoked potentials and flash visual evoked potentials in cats.

OBJECTIVE: To document normal values for air- and bone-conducted brainstem auditory evoked potentials (BAEP) and for flash visual evoked potentials (VEP) in cats. ANIMALS: 10 mixed-breed cats (5 males) with normal physical, neurologic, otoscopic, and funduscopic examination results. PROCEDURE: BAEP in response to air- and bone-conducted click stimuli and VEP in response to flash stimuli were recorded to document species normative data. Mean and SD values were calculated for amplitudes and latencies of 4 peaks in the BAEP in response to air- and bone-conducted stimuli, and for latencies to 5 peaks and the 4 associated peak-to-peak amplitudes in the VEP. RESULTS: BAEP peak latencies increased and peak amplitudes decreased with decreasing stimulus intensity. Latencies were shorter for bone-conducted stimuli owing to the shorter transit time to the cochlea through bone, compared with air, but there were no differences for interpeak latencies. The BAEP and VEP recordings were similar to those reported for cats in other reports and were similar to those seen in other species. CLINICAL RELEVANCE: Normative data will permit performance of noninvasive electrodiagnostic evaluation of feline auditory and visual systems.

Aetiology, prevalence and diagnosis of deafness in dogs and cats.

Peripheral deafness may be inherited or acquired, congenital or later-onset, and sensorineural or conductive. The most commonly observed forms are inherited congenital sensorineural, acquired later-onset sensorineural (ototoxicity, presbycusis) and acquired later-onset conductive (chronic otitis externa/media). In most dog and cat breeds inherited congenital sensorineural deafness results from perinatal degeneration of the stria vascularis, the vascular bed of the outer wall of the cochlear duct, which leads to hair cell degeneration. The strial degeneration appears to result from the absence of melanocytes, but their function in this structure is unknown. Ototoxicity may result from any of a large number of drugs and chemicals that directly or indirectly destroy cochlear hair cells. The effects are dose-dependent and in rare cases reversible. The most commonly recognized ototoxic drugs are the aminoglycoside antibiotics. Presbycusis, the ageing-related progressive hearing loss unattributable to other causes, is sensorineural but may also include mechanical changes in the tympanum and ossicles. Hearing aids may be accepted by some dogs as long as some residual function remains. Breeds reported to have been affected by congenital sensorineural deafness are listed and those with the highest prevalence are noted. Methods for diagnosis of deafness are described.

Ototoxicity assessment of a gentamicin sulfate otic preparation in dogs.

Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment. Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations.