Real-time PCR genotyping assay for canine trapped neutrophil syndrome and high frequency of the mutant allele in Border collies

Trapped neutrophil syndrome is an autosomal recessive inherited neutropenia in Border collies. The causative mutation is a 4 base pair deletion in exon 19 of the canine VPS13B gene. In this study, a real-time PCR assay was developed and a genotyping survey was carried out in Border collies in Japan. The carrier frequency was 11.1%, suggesting that the mutant allele frequency is high enough to warrant measures to control and prevent the disease.     

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members'' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.     

Spontaneous aortic dissecting hematoma in two dogs.

This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.     

Chronic intestinal pseudo-obstruction in a dog

SUMMARY A three-year-old neutered female Border Collie was presented with in-appetence, vomiting and diarrhoea. Abdominal radiographs revealed an obstructive pattern but no physical obstruction was evident at laparotomy. A diagnosis of chronic intestinal pseudo-obstruction was made based on histopathological changes in intestinal biopsies. Treatment was unsuccessful and the dog deteriorated progressively until euthanased five weeks after presentation.     

Radicular cyst of the premaxilla in a dog

A 13-year-old, male/neutered Border Collie dog was diagnosed with a radicular cyst of the left premaxilla. Tooth extraction and curettage of the lesion resulted in a positive clinical outcome 6-months following treatment.     

Vesicular cutaneous lupus erythematosus in a Border Collie in New Zealand

A 3-year-old Border Collie was initially presented for a small ulcerative lesion on the left axilla. The lesion failed to respond to conservative treatment with antibiotics, and the dog was re-presented one week later with ulcerative lesions involving the inguinal and axillary areas bilaterally. Histology of a biopsy of these lesions revealed a lymphocytic ulcerative interface dermatitis. Apoptosis and degeneration of basaloid cells was evident, with clefting along the dermo–epidermal junction. Vesicular cutaneous lupus erythematosus was diagnosed. The dog was treated with prednisone and azathioprine, resulting in complete remission of signs. However, recurrence occurred when drugs were tapered, necessitating ongoing treatment. Vesicular cutaneous lupus erythematosus has been described in North America in Rough-coated Collies and Shetland Sheepdogs. However, in Australasia, it is most commonly observed in Border Collies.     

Haplotype analysis of the MDR1 flanking region in the dog breed Elo

A deletion mutation in the canine multidrug resistance (MDR1) gene provokes drug sensitivity in several dog breeds from the Collie lineage. A haplotype of four microsatellites containing this mdr1-1Delta mutation was conserved among affected breeds. In this study, we analysed the haplotypes of the MDR1 flanking region of 177 dogs of the breed Elo which is composed of several dog breeds including the Old English sheepdog from the Collie lineage. We detected a haplotype in the Elo breed which had previously been associated with the mutant mdr1-1Delta allele in Old English sheepdogs. Using a regression analysis for the probability of the haplotype on the proportion of genes of the founder breeds, we could exclude the Old English sheepdog as origin of this haplotype for the Elo breed. The MDR1 flanking region could be traced back to the Japanese Spitz as one of the founder dog breeds of the Elo and thus, the introgression of the mdr1-1Delta mutation into the dog breed Elo through the Collie lineage is very unlikely.     

Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie

An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog.     

Retinal Disease in the N.Z. Working Dog

Sir, — It may be of interest to some rural practitioners, having an upsurge in requests for opthalmoscopic examinations of working dogs, to know that at present this practice is engaged in examinations at the National dog trials. Retinal disease is an increasing problem in both Huntaways and Heading dogs in this country. This is probably a result of the extensive use of selected strains and the tendency for the breeds to become more uniform with farmers keeping fewer better-bred dogs. Work on this complex condition is however in its infancy, and a great deal is yet to be resolved. At this stage histological sectioning suggests an inflammatory component, but computer pedigree analysis suggests a heretibility of 0.33 — 0.40. In the main the condition is not analogous to central P.R.A. present in the British Border Collie, despite its ancestral contribution particularly to the Heading dog.     

Presentation and management of trapped neutrophil syndrome (TNS) in UK border collies

Three UK bred Border collie puppies were presented for investigation of pyrexia and severe lameness with associated joint swelling. Investigations revealed neutropenia, radiographic findings suggesting metaphyseal osteopathy, and polyarthritis and all dogs were subsequently confirmed with trapped neutrophil syndrome. Clinical improvement was seen after treatment with prednisolone and antibiotics and the dogs all survived to adulthood with a good short‐ to medium‐term outcome. Trapped neutrophil syndrome is an important differential diagnosis for young Border collie dogs in the UK presenting with pyrexia, neutropenia and musculoskeletal signs.     

Use of a point-of-care urine drug test in a dog to assist in diagnosing barbiturate toxicosis secondary to ingestion of a euthanized carcass

Objective – To describe a case of barbiturate toxicosis in a dog secondary to ingestion of a previously buried euthanized goat carcass and to discuss the utility of urine drug testing in diagnosing barbiturate toxicosis.
Case Summary – A 6-year-old neutered male Border Collie was presented to a university veterinary teaching hospital for evaluation of ataxia and acute collapse. Past pertinent history included Addison's disease that had been managed for 1 year. A companion dog was seen 12 hours earlier chewing on the partially decomposed head of a goat that had been euthanized 47 days previously and buried on the owner's property. The dog was laterally recumbent, unresponsive to stimuli, and hypothermic on physical examination. Initial blood work revealed hyponatremia and hyperkalemia, with a Na/K ratio of 18.5. The dog was volume resuscitated and received an injection of dexamethasone sodium phosphate due to a suspected Addisonian crisis. Despite this treatment, the dog remained laterally recumbent and unresponsive to stimuli. A urine drug screen was performed and was positive for barbiturates. A diagnosis of barbiturate toxicosis secondary to ingestion of a euthanized goat carcass was made. The dog was treated supportively over 12 hours with IV fluids and activated charcoal. The dog was able to walk 11 hours after presentation and was subsequently discharged from the hospital.
New or Unique Information Provided – Urine drug testing is a fast, easy, and point-of-care test that may be useful in dogs to assist in the diagnosis of barbiturate intoxication. Proper disposal of euthanized animals is necessary to prevent toxicosis and possible death of companion animals and wildlife.     

Novel genotyping assay for the nt230 (del4) ABCB1 gene mutation and its allele frequency in Border Collie dogs in Mexico

A 4-bp deletion in the ATP-binding cassette subfamily B member 1 (ABCB1) gene, also referred to as the multidrug resistance gene (MDR1), produces stop codons that cause premature termination of P-glycoprotein 1 (P-gp) synthesis. Dogs with the homozygous mutation do not express functional P-gp, which increases their sensitivity markedly to many common veterinary drugs. We detected the nt230 (del4) ABCB1 mutation in Border Collie dogs in western Mexico with a simple and affordable primer-introduced restriction analysis PCR (PIRA-PCR). PIRA-PCR clearly identified all genotypes in our sample of 104 dogs. Genotype frequencies were 0.952 (wild/wild), 0.029 (wild/mut) and 0.019 (mut/mut). Allele frequencies were 0.033 (mutant alleles) and 0.966 (wild-type alleles). In this small subset of the Mexican dog population, we found a higher prevalence of the nt230 (del4) MDR1/ABCB1 gene mutation than reported in other countries.     

Analysis of the canine mdr1-1Delta mutation in the dog breed Elo

A deletion mutation in the canine multidrug resistance gene, MDR1, is associated with drug sensitivity. This was shown for several purebred dog breeds from the Collie lineage such as the Collie (rough-coated and smooth-coated), the Australian Shepherd and the Old English sheepdog. To determine whether the mdr1-1Delta mutation could be found in the newly bred German dog breed Elo which is based amongst other breeds on Old English sheepdogs, 177 blood samples representative for the Elo breed were collected. After DNA extraction, a polymerase chain reaction-based method with subsequent polyacrylamide gel electrophoresis was used for detection of the mdr1-1Delta mutation. The mdr1-1Delta allele was not observed in the Elos investigated. The probability that the mdr1-1Delta allele originated in the Old English sheepdog breed is segregating in the Elo population was estimated at 3.68 x 10(-17).     

Corneal squamous cell carcinoma in a Border Collie

A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.     

Necrotising fasciitis associated with Escherichia coli in a dog

CASE HISTORY: Lameness and limb pain associated with a laceration in the inner thigh of a Border Collie dog progressed over 4 days to extensive necrosis of the full-thickness of skin and subcutaneous (S/C) tissue. A successful outcome was achieved using surgical debridement and intensive supportive care, followed by limited local closure, axial pattern flap development, and free skin grafting. CLINICAL FINDINGS: Clinical findings included severe pain, depression, pyrexia and hypoalbuminaemia, and full-thickness loss of skin from the caudal thigh to the hock. Histopathologically, debrided tissue showed extensive necrosis of the dermis, adipose and muscle tissues, and the presence of numerous Gram-negative rods. Escherichia coli was cultured from deep tissue samples. DIAGNOSIS: Necrotising fasciitis (NF) associated with E. coli infection. CLINICAL RELEVANCE: NF associated with E. coli has not been previously reported in dogs. The importance of early diagnosis and surgical debridement is noted and the relevant medical literature is reviewed.     

Collie eye anomaly in Hokkaido dogs: case study

Objective To describe a Hokkaido dog, one of the traditional Japanese breeds that was affected by Collie eye anomaly (CEA), and to report the genotype of this dog and the Hokkaido dog allelic frequency of the CEA‐associated mutation. Case A nine‐month‐old intact female Hokkaido dog without any obvious visual disturbance was diagnosed ophthalmoscopically with CEA. Severe choroidal hypoplasia was observed in the bilateral temporal area adjacent to the optic nerve head, appearing as whitish areas. Therefore, the dog was suspected of possessing the CEA‐associated mutation that was previously reported as an intronic 7.8‐kilo base deletion in the canine NHEJ1 gene. Procedures SYBR Green‐based real‐time PCR with a melting curve analysis, conventional PCR with agarose gel electrophoresis, and direct DNA sequencing were carried out to determine the genotype of the dog. Furthermore, a preliminary genotyping survey was carried out in 17 Hokkaido dogs from three kennels using the real‐time PCR method, and the pedigree relationships were analyzed using their pedigree papers. Results The Hokkaido dog affected by CEA was proven to possess the CEA‐associated mutation. Of these 17 Hokkaido dogs, 12 dogs were heterozygous carriers and five dogs were affected by this mutation. The preliminary genotyping survey and pedigree analysis demonstrated that the allelic frequency of the CEA‐associated mutation is very high in Hokkaido dogs. Conclusion These data suggest that the Hokkaido breed is highly susceptible to CEA because of the known CEA‐associated mutation much like the Collie‐related breeds.     

Reactive histiocytosis of the orbit and posterior segment in a dog

We present a case of reactive histiocytic disease involving the orbit, optic nerve, retina, and choroid in a Border Collie dog initially presenting for vision loss. Long-term partial return of vision has been achieved with systemic immunosuppression. Anterior segment and ocular surface manifestations of reactive histiocytic disease in dogs are relatively common. Posterior segment and orbital involvement, however, are minimally documented in the existing literature. To the authors' knowledge, this is the first report of disease confined to the orbit and posterior segment as well as the first report of vision loss as a presenting complaint for reactive histiocytic disease. Clinical, magnetic resonance imaging, cytologic, and histopathologic findings are reviewed.     

Coma and respiratory failure due to moxidectin intoxication in a dog

Objective: To describe the clinical consequences following ingestion by a dog of a moxidectin‐containing equine deworming product. Few reports exist concerning the treatment and outcome of severe moxidectin toxicity. Treatment, known factors influencing intoxication, and prognosis are reviewed. Case summary: A 10‐month‐old female Border Collie ingested an unknown quantity of a moxidectin‐containing equine deworming product several hours before presentation. Severe neurological signs subsequently developed and included: ataxia, seizures, coma, and respiratory failure. The dog was treated with supportive care including intravenous fluids, activated charcoal, and positive pressure ventilation. Normal spontaneous respiration returned in 34 hours and the patient was discharged 58 hours after ingestion. Full recovery occurred within 1 week of intoxication. New information provided: This report describes moxidectin intoxication and associated respiratory failure in a dog that required mechanical ventilation. The dog's recovery was rapid. Despite severity of signs, the prognosis for patients with moxidectin intoxication is good with appropriate supportive care.     

Bilateral patellar fracture in a dog

A 4-year-old Border Collie bitch was presented with a transverse fracture of both patellae. The relevant clinical findings and subsequent surgical treatment of the fractures are described. The occurrence and management of patellar fractures in dogs are discussed.