Clinical and Electrophysiological Characterization of Myokymia and Neuromyotonia in Jack Russell Terriers

Background: Generalized myokymia and neuromyotonia (M/NM) in Jack Russell Terriers (JRTs) is related to peripheral nerve hyperexcitability syndrome in humans, a symptom complex resulting from diverse etiologies. Objective: Clinical and electrodiagnostic evaluation is used to narrow the list of possible etiological diagnoses in JRTs with M/NM. Animals: Nine healthy JRTs and 8 affected JRTs. Methods: A prospective study was conducted comparing clinical and electrophysiological characteristics in 8 JRTs affected by M/NM with 9 healthy JRT controls. Results: All affected dogs except 1 had clinical signs typical of hereditary ataxia (HA). In 6 dogs, neuromyotonic discharges were recorded during electromyogram. Motor nerve conduction studies showed an axonal neuropathy in only 1 affected dog. Compared with controls, brainstem auditory‐evoked potentials (BAEP) showed prolonged latencies (P < .05) accompanied by the disappearance of wave components in 3 dogs. Onset latencies of tibial sensory‐evoked potentials (SEP) recorded at the lumbar intervertebral level were delayed in the affected group (P < .001). The BAEP and SEP results of the only neuromyotonic dog without ataxia were normal. Conclusions and Clinical Importance: The BAEP and spinal SEP abnormalities observed in JRTs with M/NM were associated with the presence of HA. Therefore, these electrophysiological findings presumably arise from the neurodegenerative changes characterizing HA and do not directly elucidate the pathogenesis of M/NM. An underlying neuronal ion channel dysfunction is thought to be the cause of M/NM in JRTs.     

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.     

A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds

Background

Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers.

Findings

Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers.

Conclusions

A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as “hereditary ataxia” in Fox Terriers and “spinocerebellar ataxia with myokymia, seizures or both” in the Russell group of terriers.     

A Homozygous KCNJ10 Mutation in Jack Russell Terriers and Related Breeds with Spinocerebellar Ataxia with Myokymia,Seizures, or Both

Background

Juvenile‐onset spinocerebellar ataxia has been recognized in Jack Russell Terriers and related Russell group terriers (RGTs) for over 40 years. Ataxia occurs with varying combinations of myokymia, seizures, and other signs of neurologic disease. More than 1 form of the disease has been suspected.

Hypothesis/Objectives

The objective was to identify the mutation causing the spinocerebellar ataxia associated with myokymia, seizures, or both and distinguish the phenotype from other ataxias in the RGTs.

Animals

DNA samples from 16 RGTs with spinocerebellar ataxia beginning from 2 to 12 months of age, 640 control RGTs, and 383 dogs from 144 other breeds along with the medical records of affected dogs were studied.

Methods

This case‐control study compared the frequencies of a KCNJ10 allele in RGTs with spinocerebellar ataxia versus control RGTs. This allele was identified in a whole‐genome sequence of a single RGT with spinocerebellar ataxia and myokymia by comparison to whole‐genome sequences from 81 other canids that were normal or had other diseases.

Results

A missense mutation in the gene coding for the inwardly rectifying potassium channel Kir4.1 (KCNJ10:c.627C>G) was significantly (P < .001) associated with the disease. Dogs homozygous for the mutant allele all had spinocerebellar ataxia with varying combinations of myokymia and seizures.

Conclusions and Clinical Importance

Identification of the KCNJ10 mutation in dogs with spinocerebellar ataxia with myokymia, seizures, or both clarifies the multiple forms of ataxia seen in these breeds and provides a DNA test to identify carriers.     

Hereditary ataxia in the Jack Russell Terrier--clinical and genetic investigations

Hereditary ataxia in the Jack Russell Terrier (JRT) is characterized by a gait disturbance with symmetric generalized ataxia and hypermetric and spastic movements. Histopathology shows a disease of the entire central nervous system, predominantly an axonopathy. In the present study, 35 clinically affected dogs were examined. Gait abnormalities began at 2-9 months of age. Generalized seizures occurred in 13 dogs in addition to the ataxia, and 7 dogs developed respiratory distress. Brain stem auditory-evoked potentials (BAEPs) were abnormal in 4 of 8 examined dogs, in which only waves I and II were detected. Abnormal BAEPs suggest the possibility of hereditary ataxia in the JRT. Investigations regarding the mode of inheritance were performed by complex segregation analyses on 3 pedigrees with a total of 115 JRTs (27 clinically affected dogs and 88 unaffected littermates and ancestors). Different modes of inheritance were tested, including monogenic, mixed, and polygenic models, as well as a model with environmental effects only. Models with genetic effects explained the data significantly better than the environmental model. The monogenic model had to be rejected in this study because of an insufficient match of data when compared to that of the most general model. The polygenic and mixed major gene models explained the pedigree data best and therefore have to be regarded as possible hypotheses for the mode of inheritance of hereditary ataxia in the JRT. The polygenic model proved best suited to explain the segregation pattern in the JRT, because it had the fewest number of parameters.     

Clinical and histopathological features and prognosis of gastrointestinal adenocarcinomas in Jack Russell Terriers

There has been an increase in the number of Jack Russell Terriers (JRTs) diagnosed with adenomas and adenocarcinomas of the gastrointestinal tract in Japan. This study retrospectively investigated the clinical and histopathological features and prognosis of adenocarcinomas arising in the gastrointestinal tract in JRT dogs. Seven JRTs and 39 dogs of other breeds diagnosed with gastrointestinal adenocarcinoma were included in the study. The most common sites of gastrointestinal adenocarcinoma in JRTs were the pylorus and rectum. On histopathological examination, these adenocarcinomas showed a papillary or tubular growth pattern, and the lesions were confined within the mucosal epithelium and poorly invasive. Among all dogs with gastric adenocarcinoma, the median survival time (MST) for five of the JRTs could not be determined because more than half of the cases remained alive, while the MST for nine non-JRT dogs was 34 days. Among all dogs with adenocarcinoma in the large intestine, the MST for three of the JRTs could not be determined, while the MST for nine non-JRT dogs was 1,973 days. The difference in MST between JRT and non-JRT dogs with gastric adenocarcinoma was significant (P=0.0220). Since gastrointestinal adenocarcinomas in JRTs show distinct characteristics with respect to their clinical features, treatment course, and prognosis, a different surgical and medical treatment plan should be considered compared to the management of gastrointestinal adenocarcinomas in other dog breeds.     

Recurrent demyelination and remyelination in 37 young Bengal cats with polyneuropathy

Background: With the exception of diabetic neuropathy, polyneuropathy associated with hyperchylomicronemia, and a few inherited polyneuropathies, peripheral neuropathies are poorly characterized in cats. A chronic polyneuropathy is described in a cohort of young Bengal cats. Objective: To characterize the clinical and histopathological features of a chronic‐relapsing peripheral neuropathy in young Bengal cats. Animals: Thirty‐seven young Bengal cats with clinical weakness consistent with peripheral neuropathy. Methods: Bengal cats were included in this study after a diagnosis of polyneuropathy was confirmed by muscle and peripheral nerve biopsy specimens. Pathological changes were characterized at the light and electron microscopic level and by morphometry. Clinical information and long‐term outcome from case records of Bengal cats with histologically confirmed peripheral neuropathy were then assessed. Results: Nerve fiber loss within distal intramuscular nerve branches was a consistent finding in young Bengal cats with polyneuropathy. The most common abnormalities in peripheral nerve biopsies included inappropriately thin myelin sheaths and thinly myelinated fibers surrounded by supernumerary Schwann cell processes, indicative of repeated cycles of demyelination and remyelination. Recovery was common. Response to treatment could not be determined. Conclusions and Clinical Importance: A chronic‐relapsing form of polyneuropathy associated primarily with episodes of demyelination and remyelination was identified in young Bengal cats. The prognosis for recovery is good, although relapses are possible and there can be residual motor deficits.     

Effect of Sanguinarine on Active Capacity of Isolated Rat Uterine Smooth Muscle in vitro and Its Mechanism

The study was aimed to explore the effects of the sanguinarine on activity of isolated rat uterine smooth muscle in vitro. The effect of the sanguinarine on activity of the isolated myometrium of non-pregnant Sprague-Dawley rats eight weeks old was recorded by BL-420F four channels physiological recorder. Four antagonists, atropine sulfate, ranitidine hydrochloride, propranolol hydrochloride and diphenhydramine hydrochloride were used to study their mechanism, respectively. The results showed that sanguinarine and Yuan hu painkillers markedly inhibited the frequency, amplitude and activity of uterine contractions induced by oxytocin injection (P<0.05). The inhibitory effect of sanguinarine on uterine muscle contractions was blocked after using diphenhydramine hydrochloride (H₁-receptor antagonist) and ranitidine hydrochloride (H₂-receptor antagonist). However, after using atropine sulfate (M-receptor antagonist) and propranolol hydrochloride (β-receptor antagonist), sanguinarine also significantly inhibited the contractions of rat uterine smooth muscle (P<0.05). It was concluded that the effect of sanguinarine on activity of uterine smooth muscle in rats was mainly associated with H₁ receptor or H₂ receptor but not M receptor or β receptor.     

血根碱对大鼠离体子宫平滑肌收缩的影响及其机制研究

试验旨在研究血根碱对大鼠离体子宫平滑肌活动的影响。分离8周龄SD雌性未孕大鼠子宫平滑肌,通过BL-420F生物信号采集系统记录子宫平滑肌收缩频率和收缩幅度,计算子宫平滑肌活力。以硫酸阿托品、盐酸普萘洛尔、盐酸苯海拉明及盐酸雷尼替丁为阻断剂,观察血根碱对子宫平滑肌M、β、H₁、H₂受体的关系,探讨血根碱对子宫平滑肌的作用机制。结果显示,血根碱组和元胡止痛片组对缩宫素所致大鼠离体子宫平滑肌收缩频率、收缩幅度和活力均有显著的抑制作用（P<0.05）;应用H₁受体阻断剂苯海拉明和H₂受体阻断剂雷尼替丁后,血根碱对子宫平滑肌抑制作用基本被阻断,而应用M受体阻断剂阿托品,β受体阻断剂普萘洛尔后,血根碱对子宫平滑肌收缩仍具有显著的抑制作用（P<0.05）。综上所述,血根碱对大鼠子宫平滑肌活力具有显著的抑制作用,可能是通过抑制H₁、H₂受体实现,与M、β受体无关。     

Cataracts in Labrador Retriever and Jack Russell Terrier From the United Kingdom: A Two-Year Retrospective Study

Cataracts are among the most common ocular diseases, and are a leading cause of vision loss in humans and dogs. Jack Russell Terriers (JRT) and Labrador Retrievers (LR) are among the most popular canine breeds in the United Kingdom, and also among the most affected by cataracts.This study aimed to analyze the clinical features and the surgical outcome of cataracts in JRT and LR in an ophthalmologic reference Veterinary Hospital in the United Kingdom. For that purpose, medical records from JRT and LR diagnosed with cataracts between January 2015 and December 2016 were retrospectively evaluated. Data related to identification, clinical history, preoperative features, and surgical outcomes were analyzed.Forty-four dogs (81 eyes), including 26 JRT and 18 LR, were enrolled in the study. Mean ages were 10.2 ± 3.2 years in JRT and 8.5 ± 3.7 years in LR. Twenty-eight (63.6%) were females and 16 (36.4%) were males. Most dogs (84.1%) presented with bilateral cataracts. Nuclear and cortical cataracts were the most prevalent type in both breeds (JRT: n?=?30, 61.2%; LR: n?=?16, 50.0%), although subcapsular cataracts were also frequent in LR (n?=?10, 31.3%). Significant differences in cataract location within the lens were detected between the two breeds (P?=?.002).Senile in JRT (n?=?7) and genetic in LR (n?=?7) were the most common etiologies. Concomitant ocular lesions were more frequent in dogs presented with cataracts in advanced stages, and included lens (n?=?18; JRT: n?=?15; LR: n?=?3) and retinal alterations (n?=?8; JRT: n?=?2; LR: n?=?6), and glaucoma (n?=?6; JRT: n?=?5; LR: n?=?1). Thirty-three animals (75.0%, 51 eyes) were submitted to phacoemulsification with intraocular lens placement. Of these, 28 eyes (54.9%; JRT: n?=?21; LR: n?=?7) were visual, 19 eyes (37.3%; JRT: n?=?11; LR: n?=?8) presented impaired vision and four eyes (7.8%; JRT: n?=?0; LR: n?=?4) were blind at last clinical record. Postoperative complications were detected in 11 eyes (21.6%), and were more frequent in dogs presented with cataracts in advanced stages.These results and the multifactorial nature of cataracts call for further studies to identify and characterize the variables in a broader assessment, including other breeds and influencing factors.     

Preliminary Study on Age- and Sex-Dependent Alterations in the Composition of Skeletal Muscle Fibers of Brasileiro de Hipismo Horses

The aim of this work was to characterize the distribution of myofibers in the gluteus medius muscle of inactive horses of the Brasileiro de Hipismo (BH) breed at different ages by means of histochemical analyses, according to sex and depth of the biopsy. A total of 78 inactive horses (9 castrated males, 35 stallions, and 34 females) of the BH breed, aged 1 to 4 years, were used. A percutaneous muscle biopsy was obtained with a 6.0-mm Bergström-type needle, which allowed the removal of muscle fragments at depths of 20 and 60 mm. Myofiber types were determined based on myofibrillar adenosine triphosphatase (mATPase) and nicotinamide dinucleotide tetrazolium reductase (NADH-TR) techniques. Morphometry of the fibers was determined based on cross-sectional area (CSA), mean frequency (F), and relative cross-sectional area (RCSA). The current study demonstrated that BH horses 3 and 4 years of age show a greater percentage of, and area occupied by, type IIA fibers and lower percentage of type IIX fibers in the gluteus medius muscle compared with horses 1 and 2 years of age. No difference was found between sexes in the frequency of and area occupied by the different fiber types at any of the depths and ages studied. In this study, females showed a greater CSA for all fibers in comparison with males, at 1 year of age. The results of the current study indicate that the gluteus medius muscle of inactive BH horses shows modifications in its structural and biochemical composition during the growth of the animals, leading to a better oxidative capacity.     

Characterization and mode of inheritance of a paroxysmal dyskinesia in Chinook dogs

Background: Paroxysmal dyskinesias are episodes of abnormal, involuntary movement or muscle tone, distinguished from seizures by the character of the episode and lack of seizure activity on ictal EEG. Hypothesis: Paroxysmal dyskinesia is an inherited, autosomal recessive disorder in Chinook dogs. Animals: Families of Chinook dogs with paroxysmal dyskinesia. Methods: Pedigrees and medical histories were reviewed for 299 Chinook dogs. A family of 51 dogs was used for analysis. Episodes were classified as seizures, paroxysmal dyskinesia, or unknown, and segregation analysis was performed. Results: Paroxysmal dyskinesia was identified in 16 of 51 dogs and characterized by an inability to stand or ambulate, head tremors, and involuntary flexion of 1 or multiple limbs, without autonomic signs or loss of consciousness. Episode duration varied from minutes to an hour. Inter‐ictal EEGs recorded on 2 dogs with dyskinesia were normal. Three dogs with dyskinesia also had generalized tonic‐clonic seizures. One of 51 dogs had episodes of undetermined type. Phenotype was unknown for 6 of 51 dogs, and 28 dogs were unaffected. Segregation was consistent with an autosomal recessive trait. Conclusions and Clinical Importance: This movement disorder is prevalent in the Chinook breed, and consistent with a partially penetrant autosomal recessive or polygenic trait. Insufficient evidence exists for definitive localization; episodes may be of basal nuclear origin, but atypical seizures and muscle membrane disorders remain possible etiologies. The generalized seizures may be a variant phenotype of the same mutation that results in dyskinesia, or the 2 syndromes may be independent.     

猪骨骼肌纤维的生长与营养调控

肌纤维是肌肉组织的最主要组成部分,可根据其代谢特性、收缩功能和肌球蛋白重链多态性进行不同分类.肌纤维类型及组成与猪肉品质密切相关,因此了解肌纤维的生长发育规律、类型分化与转化及其营养调控,对提高肌肉生长效率和改善肉品质具有重要意义.