OBJECTIVE: To describe multiple congenital ocular anomalies in three litters of Jack Russell Terrier puppies.
METHODS: Seven purebred Jack Russell Terrier puppies from three related litters and their four parents.
METHODS: Medical records of the puppies and their parents were evaluated. All dogs underwent a complete ophthalmic examination, followed by bilateral ocular ultrasonography in two of the puppies with complete corneal opacity. One eye from an affected puppy was subjected to histopathology. A complete database of pedigrees was built, and individual inbreeding was evaluated.
RESULTS: The most commonly diagnosed ocular anomalies in the puppies were: various anomalies of the fundus (12/14 eyes); microphthalmia (10/14 eyes); sclerocornea (8/14 eyes); and persistent pupillary membranes (7/14 eyes). Six out of seven puppies had at least two ocular abnormalities, and only one puppy was normal. Four out of seven puppies had sclerocornea, a particular corneal opacity to date described only in Spanish Podenco dogs. No ocular abnormalities were found in the parents examined (4/4). Analysis of the pedigrees showed that all the puppies and two parents were inbred, and the individual values of the inbreeding puppies were greater than 6.25% in two litters.
CONCLUSIONS: Inbreeding with closely related Jack Russell Terriers may result in severe congenital eye abnormalities in puppies.

Jack Russell terriers (JRTs) with gastrointestinal (GI) neoplastic polyps have been recently reported to harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT], in the heterozygous state, which indicates that this disease is an autosomal dominant hereditary disorder. Many individual cases of this disease have been observed in clinical practice; however, familial transmission has not been demonstrated due to the difficulty in tracing the family members of household dogs, especially after the disease\'s onset in adulthood. Recently, we encountered two cases of GI polyposis in maternal half sisters. These two cases facilitated the identification of additional relatives spanning three generations, including parents, full and half siblings of the dam (aunt and uncle), littermate and non-littermate siblings, and a nephew. Genetic analysis revealed that 11 of the 14 examined JRTs in this family carried the heterozygous germline APC variant, and eight dogs with the variant already had a current and/or past medical history of GI neoplastic polyps. Some cases in the family showed significantly more severe disease phenotypes than those initially reported, suggesting that the severity of this disease can vary considerably among individuals. Moreover, familial aggregation of severe cases suggested that the genetic modifier involved in increasing severity may have been transmitted in this family in addition to the germline APC variant. Furthermore, in addition to this family, we reported two other families of JRTs affected by hereditary GI polyposis that consisted of five full and half siblings and a mother-daughter pair, respectively. These findings unequivocally establish the transgenerational transmission of hereditary GI polyposis associated with the germline APC variant in JRT lineages.

Hereditary GI polyposis in JRTs is a novel hereditary disease characterized by the development of solitary and multiple polypoid tumors, predominantly in the stomach and/or colorectum. Our recent study indicated that JRTs with GI neoplastic polyps harbor an identical germline variant in the APC gene, c.[462_463delinsTT], in a heterozygous state. Unlike sporadic cases, dogs afflicted with hereditary GI polyposis can be expected to have a prolonged survival time, as hereditary tumors are noninvasive. Since the discovery of this disease, the number of newly diagnosed cases in Japan has increased, allowing us to update the clinical and pathological features and provide a large number of diagnostic images. The present clinical case series study employing various diagnostic imaging techniques revealed that some of the cases harbored tumors in the small intestine in addition to the stomach and colorectum. Moreover, although rare, hereditary GI cancers can progress to the advanced stage and develop systemic metastasis, similar to sporadic GI tumors. These findings indicate that there is a wider range of variation in disease severity than was initially recognized. Our results can contribute to the accurate diagnosis of hereditary GI polyposis in clinical practice, pathological examinations, and future research.

BACKGROUND: Cases of gastrointestinal (GI) neoplastic polyps in Jack Russell Terriers (JRTs) have increased in Japan since the late 2000s. We recently demonstrated that JRTs with GI polyps heterozygously harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT]; therefore, this is an autosomal dominant hereditary disease. We conducted a molecular epidemiological study to explore the current frequency of the APC variant in JRTs in Japan and the breed distribution of this disease.
RESULTS: Peripheral blood samples from 792 JRTs were collected at 93 veterinary hospitals in Japan in 2020. Using an established polymerase chain reaction-restriction fragment length polymorphism assay, the germline APC variant was detected in 15 JRTs, with an overall frequency of 1.89%. The frequency was not significantly different for sex, age, and coat type criteria. Notably, the variant carriers had a current or previous history of GI neoplastic polyps, providing further evidence of the association of the germline APC variant with GI polyposis. Pedigree analysis of carrier dogs revealed that the germline APC variant was no longer confined to a few specific families but was widely spread among JRTs in Japan. Furthermore, some ancestors of the carriers were from Australia or New Zealand, suggesting the possible presence of carriers in countries other than Japan. Next, we retrospectively investigated the germline APC variant status of dogs with GI epithelial tumors using genomic DNA samples extracted from archived pathological specimens (28 purebred dogs of 14 breeds and four mixed-breed dog), as well as those stored in a canine genome bank (38 dogs of 18 breeds and a mixed-breed dogs). In total, 66 purebred dogs of 25 breeds, including another four JRTs, and five mixed-breed dogs were examined. While three variant carriers were found in JRTs, the germline APC variant was not detected in any of the other breeds.
CONCLUSIONS: The current frequency of the germline APC variant was approximately 2% in JRTs in Japan and the frequency remained roughly flat during the last 15 years. In addition, hereditary GI polyposis associated with the variant was virtually specific to JRTs.

Abstract  A new, possibly breed associated, vasculitis of Jack Russell Terriers is described. Lesions include alopecia and focal crusted ulcers of the distal extremities and bony prominences. Histopathological lesions include single cell necrosis of the epithelium, pigmentary incontinence, leucocytoclastic vasculitis and ischaemic degeneration of hair follicles. Dermal oedema and an infiltrate of lymphocytes and/or macrophages are often seen. Clinically and histopathologically the disease most closely resembles dermatomyositis of Collies and Shetland sheepdogs but the obvious breed discrepancy makes systemic lupus erythematosus the most likely differential diagnosis. Dapsone and anti-inflammatory doses of prednisone have proved to be satisfactory treatments. Résumé- Une nouvelle dermatose à prédisposition raciale, de type vascularite est décrite chez des jack russel terriers. Les lésions cliniques incluent une alopécie, des ulcèrations focales et croûteuses des extrémités distales et des points de pression. Les lésions histolopathologiques montrent des nécroses isolées des kératinocytes, une incontinence pigmentaire, une vascularite leucocytoclasique et une dégénérescence ischémique des follicules pileux. Un oedème dermique et une infiltration lymphocytaire et/ou macrophagique sont également observés. Sur les plans clinique et histopathologique, cette maladie ressemble plus aux dermatomyosites du Colley et du Shetland, mais la discordance raciale évidente fait du lupus érythémateux systémique le diagnostic différentiel le plus vraisemblable. La dapsone et la prednisone à dose antiinflammatoire sont des traitements satisfaisants. [Parker, W.M., Foster, R.A. Cutaneous vasculitis in five Jack Russell Terriers (Vascularite cutanée chez 5 jack russel terriers). Veterinary Dermatology 1996; 7: 109-115.] Resumen  Se describe una vasculitis nueva, posiblemente asociada a la raza en el terrier Jack Russell. Las lesiones incluyen alopecia y ulceraciones costrosas en las extremidades distales y en prominencias óseas. Las lesiones histopatológicas incluyen necrosis celular individual del epitelio, incontinencia pigmentaria, vasculitis leucocitoclástica y degeneración isquémica de los foliculos pilosos. Con frecuencia se observa edema dérmico y una infiltración por linfocitos y/o macrófagos. Este cuadro se asemeja clinica e histopatológicamente a la dermatomiositis de los perros Collie y Shetland pero la distancia obvia entre estas razas hace que el diagnóstico diferencial más probable sca el de lupus eritematoso sistémico. Se consiguieron tratamientos satisfactorios con Dapsona y dosis antiinflamatorias de prednisona. [Parker, W.M., Foster, R.A. Cutaneous vasculitis in five Jack Russell Terriers (Vasculitis cutánea en cinco Terriers Jack Russell). Veterinary Dermatology 1996; 7: 109-115.] Zusammenfassung- Es wird eine neue, möglicherweise rasseabhängige Vaskulitis bei Jack Russell Terriern beschrieben. Die Veränderungen bestehen in Alopezie, fokalen verkrusteten Geschwüren der distalen Extremitäten und Knochevorsprünge. Histopathologische Veränderungen bestehen in Einezelzellnekrose des Epithels, Pigmentinkontinenz, leukozytoklastischer Vaskulitis und ischämischer Degeneration der Haarfollikel. Dermales ödem und Lymphozyten- und/oder Makrophageninfiltrate werden häufig beobachtet. Klinisch und histopathologisch ähnelt die Erkrankung sehr der Dermatomyositis von Collie und Sheltie, aber die offensichtliche Rassendiskrepanz läßt den systemischen Lupus erythematosus als wahrscheinlichste Differentialdiagnose erscheinen. Dapson und entzündungshemmende Dosen von Prednison zeigten sich als ausreichende Behandlung. [Parker, W. M., Foster, R. A. Cutaneous vasculitis in five Jack Russell Terriers (Kutane Vaskulitis bei fünf Jack Russell Terriern). Veterinary Dermatology 1996; 7: 109-115.].

A prospective clinical trial was carried out in a 6-week-old male Jack Russell terrier with congenital ichthyosis to evaluate stratum corneum lipids; transmission electron microscopy of skin specimens; and clinical and dermatopathological response to vitamin A alcohol therapy. Also evaluated were the clinical, dermatopathological, and epidermal cell proliferation kinetics response to a synthetic retinoid in a dog with congenital ichthyosis.  Epidermal cell renewal time was markedly decreased compared with normal and seborrhoeic dogs. Skin specimens were characterized by severe and diffuse compact orthokeratosis that extended into the infundi-bulum of the hair follicles. The stratum granulosum was normal. On transmission electron microscopy, the stratum corneum was thickened and intercorneocyte spaces were extremely narrow. The first three corneocyte layers contained tonofilaments that were irregular, coarse and wavy. Tonofilament packing appeared more normal and regular in the fourth and fifth corneocyte layers. Outer layers of stratum corneum were extraordinarily electron-dense compared with normal. There was a decrease in stratum corneum free fatty acid and acyl-ceramide and an increase in ceramide III levels compared with three normal dogs. Three months of oral vitamin A alcohol did not result in clinical improvement, although histologically the orthokeratosis was less compact. After 6 months of oral etretinate therapy, comedones and scales were markedly less evident grossly. Although compact orthokeratosis was still present on histological examination of skin, it was less than that present at 6 weeks of age. Epidermal cell kinetics were not altered after etretinate therapy.

BACKGROUND: The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline variant in the APC gene (c.[462_463delinsTT]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC variant were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs.
RESULTS: First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC variant creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the variant site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the variant was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays.
CONCLUSIONS: In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC variant. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.

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.

BACKGROUND: Spinocerebellar ataxia also referred to as hereditary ataxia comprises different forms of progressive neurodegenerative diseases. A complex mode of inheritance was most likely in Parson Russell Terriers (PRT) and in Jack Russell Terriers (JRT). Recently, the missense mutation KCNJ10:c.627C > G was shown to be associated with the spinocerebellar ataxia (SCA) in JRT and related Russell group of terriers, whereas the missense mutation CAPN1:c.344G > A was associated with late onset ataxia (LOA) in PRT.
RESULTS: We performed a genome-wide association study (GWAS) in PRT including 15 cases and 29 controls and found a statistically strong signal in the genomic region on dog chromosome 38 (CFA38) where KCNJ10 is located. We tested the CAPN1:c.344G > A and KCNJ10:c.627C > G (Transcript XM_545752.4) mutations in a sample of 77 PRT and 9 JRT from Germany as well as further 179 controls from 20 different dog breeds. All cases and controls genotyped carried the wild-type for the CAPN1:c.344G > A mutation. Among the PRT, 17/77 (22.1 %) dogs were homozygous for the mutant KCNJ10 allele and 22/77 (28.6 %) dogs were heterozygous. Three cases of PRT had the homozygous KCNJ10 wild-type. In JRT, 1/3 cases did show the mutant KCNJ10 allele homozygous. Thus, we sequenced the KCNJ10 exons with their adjacent regions from 10 PRT and 3 JRT including the animals with imperfect co-segregation of the c.627C > G mutation. We identified a total of 45 genetic variants within KCNJ10. The most likely variant explaining the cases appeared a 1-bp-insertion in a C-stretch within exon 3 (KCNJ10:g.22141027insC). In silico analysis showed that this indel may influence the regulation of gene expression.
CONCLUSIONS: In the present study, 16/21 cases of hereditary ataxia perfectly co-segregated with the KCNJ10:c.627C > G mutation. The CAPN1:c.344G > A mutation could not be validated and seems to be a rare variant in the samples screened. Screening KCNJ10 for further mutations did result in a genetic variant explaining 2 JRT cases but further 3 cases with a non-mutant homozygous c.627C > G genotype could not be resolved. Breeders have to be aware that DNA-testing for hereditary ataxia in PRT and JRT does not capture all cases of hereditary ataxia in these dog breeds. At least one further form of hereditary ataxia not yet resolved by a mutation may occur in PRT and JRT.

Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term \'peripheral nerve hyperexcitability\' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals.