Highland White Terrier Research Articles

Analysis of gene expression in canine idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) in dogs is a rare disease of unknown aetiology, seen in terrier breeds, particularly the West Highland white terrier (WHWT). The aim of this study was to determine pulmonary gene expression in canine IPF in order to gain insights into the pathogenesis of the disease and to identify possible biomarkers. Microarray analyses were conducted to determine gene expression profiles in the lungs of dogs with IPF and control dogs of various breeds. More than 700 genes were identified as having greater than two-fold difference in expression between the two groups. The significant biological functions associated with these genes were related to cellular growth and proliferation, developmental processes, cellular movement, cell to cell signalling and interaction, and antigen presentation. Altered levels of expression were confirmed by quantitative reverse transcriptase PCR for genes encoding chemokine (C–C) ligand (CCL) 2 (+4.9 times), CCL7 (+6.8 times), interleukin 8 (+4.32 times), chemokine (C–X–C) ligand 14 (+3.4 times), fibroblast activation protein (+4.7 times) and the palate, lung and nasal associated protein (PLUNC, −25 times). Serum CCL2 concentrations were significantly higher in WHWTs with IPF (mean 628.1pg/mL, interquartile range 460.3–652.7pg/mL) than unaffected WHWTs (mean 344.0pg/mL, interquartile range 254.5–415.5pg/mL; P=0.001). The results support CCL2 as a candidate biomarker for IPF in dogs.

Erythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK

Erythrocyte pyruvate kinase (PK) deficiency is described for the first time in three apparently unrelated West Highland white terriers (WHWT) from Ireland and the UK. All three dogs were diagnosed with markedly regenerative but persistent anaemia and had been treated for presumed immune-mediated haemolytic anaemia (IMHA) before hereditary erythrocyte PK-deficiency was confirmed by breed-specific DNA mutation analysis. This hereditary erythroenzymopathy causes haemolytic anaemia and affects several canine breeds with varying degrees of severity. Although eventually causing osteosclerosis, haemosiderosis and death, PK-deficient dogs can adapt to their anaemia for many years.PK-deficiency should be considered in anaemic WHWTs worldwide particularly in dogs with haemolytic anaemia where evidence for an immune-mediated, infectious or toxic underlying cause is lacking.

Combined idiopathic chylopericardium and chylothorax treated with pericardiectomy under thoracoscopy in a dog

Summary A 22-month-old intact female West Highland White Terrier was diagnosed with idiopathic chylothorax and chylopericardium. Treatment by pericardiectomy without thoracic duct ligation was performed under thoracoscopy. After 2 weeks of postoperative care including intermittent pleural drainage, the dog recovered completely. Five years later, the dog was still healthy.

Relationships between heart rate and age, bodyweight and breed in 10,849 dogs

To evaluate relationships between heart rate and clinical variables in healthy dogs and dogs examined at a referral hospital. Clinical data were extracted from the electronic patient records of a first opinion group (5000 healthy dogs) and a referral hospital (5849 dogs). Univariable and multi-variable general linear models were used to assess associations between heart rate and clinical characteristics. Separate multi-variable models were constructed for first opinion and referral populations. In healthy dogs, heart rate was negatively associated with bodyweight (P<0.001) but was higher in Chihuahuas. The mean difference in heart rate between a 5 and 55 kg dog was 10.5 beats per minute. In dogs presenting to a referral hospital, heart rate was negatively associated with bodyweight (P<0.001) and the following breeds; border collie, golden retriever, Labrador retriever, springer spaniel and West Highland white terrier and positively associated with age, admitting service (emergency and critical care, emergency first opinion and cardiology) and the following breeds; Cavalier King Charles spaniel, Staffordshire bull terrier and Yorkshire terrier. Bodyweight, age, breed and disease status all influence heart rate in dogs, although these factors account for a relatively small proportion of the overall variability in heart rate.

The Histopathology of Idiopathic Pulmonary Fibrosis in West Highland White Terriers Shares Features of Both Non-specific Interstitial Pneumonia and Usual Interstitial Pneumonia in Man

Idiopathic pulmonary fibrosis (IPF) in West Highland white terriers (WHWTs) is a breed-related, spontaneously arising disease that is a potential animal model for IPF in man. Histopathological similarity between IPF in WHWTs and usual interstitial pneumonia (UIP), the histopathological correlate for IPF in man, has not been confirmed and histological features of non-specific interstitial pneumonia (NSIP), another form of human idiopathic interstitial pneumonia, have been reported in WHWTs with IPF. This study describes the pulmonary histopathological findings in 18 WHWTs with IPF, including lobe-specific samples in nine of the dogs. The canine lesions and their distribution pattern are compared with histopathological characteristics in samples of human UIP and NSIP. Underlying diffuse mature fibrosis, resembling human NSIP more than UIP, was seen in the lungs of all dogs with IPF. Additionally, the majority of dogs with IPF showed multifocal areas of accentuated subpleural and peribronchiolar fibrosis with occasional 'honeycombing' and profound alveolar epithelial changes, reminiscent of human UIP and not commonly seen in NSIP. Interstitial fibroblastic foci, characteristic of UIP, were not seen in WHWTs with IPF. Progressive fibrosis, with intra-alveolar organizing fibrosis alongside interstitial mature collagen deposition, was present within the more severely affected areas of lung in WHWTs with IPF. Severe pulmonary lesions were seen more commonly in the caudal than in the cranial lung lobes.

Breed predispositions in canine mast cell tumour: A single centre experience in the United Kingdom

Genetic factors play a major role in carcinogenesis. Many breeds have been reported to be predisposed to mast cell tumour (MCT) development using various methods and diverse control populations. A database of 222 dogs with MCT seen at a UK university referral hospital was compared to three control populations, namely, an insured population of UK dogs, registrations with the UK Kennel Club and other dogs seen through the same hospital. Odds ratios were calculated for each breed. Boxers, Labradors, Golden Retrievers and Staffordshire Bull Terriers appeared predisposed to MCT development. English Springer Spaniels, English Cocker Spaniels, German Shepherd Dogs, West Highland White Terriers and Cavalier King Charles Spaniels were underrepresented.

Population structure and genetic heterogeneity in popular dog breeds in the UK

There is increasing concern that reproductive isolation related to breed specifications in dogs, while maintaining genetic differences among breeds, is likely to promote breed-specific genetic disorders. This study examined genetic diversity among 13 popular dog breed groups in the UK. Most breeds showed high levels of homozygosity when compared with crossbred animals. The Boxer and West Highland white terrier showed the lowest heterozygosity, while the Jack Russell terrier group (not a registered breed in the UK) had a level of heterozygosity comparable to crossbred dogs. Analysis of genetic distance between breeds showed significantly different inbreeding coefficients for pairwise comparisons among registered breeds, with the most divergent breeds being the Boxer and West Highland white terrier. The Rottweiler and Golden retriever showed the highest levels of inbreeding. The least distinct group contained crossbred dogs. The results show that the registered breeds are subject to a 'breed barrier' which promotes reduction in genetic diversity.

MHC class II association study in eight breeds of dog with hypoadrenocorticism

Canine hypoadrenocorticism is an endocrine disorder characterised by inadequate secretion of steroid hormones from the adrenal glands. Pathology results from immune-mediated destruction of the adrenal cortex, which is similar to that seen in the human Addison's disease. Both the canine and human diseases have similar clinical presentation, with the diagnosis based on performing a dynamic adrenocorticotropic hormone stimulation test. MHC class II has previously been associated with the human and canine diseases. In the current study, we conducted an MHC class II association study in eight breeds of dog with diagnoses of hypoadrenocorticism. We demonstrated significant differences in dog leukocyte antigen (DLA) haplotype frequencies in six of these breeds: Cocker spaniel, Springer spaniel, Labrador, West Highland white terrier (WHWT), Bearded collie, and Standard poodle. In the Springer spaniel, the DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01 haplotype was significantly associated with disease risk (p = 0.014, odds ratio (OR) = 5.14) and showed a similar trend in the Cocker spaniel. This haplotype is related to one associated with hypoadrenocorticism in the Nova Scotia duck tolling retriever. Similar haplotypes shared between breeds were demonstrated, with DLA-DRB1*001:01--DQA1*001:01--DQB1*002:01 more prevalent in both affected Labrador (p = 0.0002, OR = 3.06) and WHWT (p = 0.01, OR = 2.11). Other haplotypes that have not previously been associated with the disease were identified. The inter-breed differences in DLA haplotypes associated with susceptibility to canine hypoadrenocorticism could represent divergent aetiologies. This could have implications for clinical diagnosis and future comparative studies. Alternatively, it may suggest that the gene of interest is closely linked to the MHC.

Prevalence and risk factors for canine epilepsy of unknown origin in the UK

Epidemiological evaluation of canine epilepsy is an under-researched area. The objectives of this study were to estimate prevalence and investigate risk factors for epilepsy of unknown origin (EUO) among dogs...

Proteomic analysis of bronchoalveolar lavage fluid samples obtained from West Highland White Terriers with idiopathic pulmonary fibrosis, dogs with chronic bronchitis, and healthy dogs

To evaluate protein expression in bronchoalveolar lavage fluid (BALF) obtained from West Highland White Terriers with idiopathic pulmonary fibrosis (IPF), dogs with chronic bronchitis, and healthy control dogs to identify potential biomarkers for IPF. BALF samples obtained from 6 West Highland White Terriers with histologically confirmed IPF, 5 dogs with chronic bronchitis, and 4 healthy Beagles. Equal amounts of proteins in concentrated BALF samples were separated via 2-D differential gel electrophoresis. Proteins that were differentially expressed relative to results for healthy control dogs were identified with mass spectrometry and further verified via western blotting. Expression of 6 proteins was upregulated and that of 1 protein was downregulated in dogs with IPF or chronic bronchitis, compared with results for healthy dogs. Expression of proteins β-actin, complement C3, α-1-antitrypsin, apolipoprotein A-1, haptoglobin, and transketolase was upregulated, whereas expression of lysozyme C was downregulated. Proteomics can be used to search for biomarkers and to reveal disease-specific mechanisms. The quantitative comparison of proteomes for BALF obtained from dogs with IPF and chronic bronchitis and healthy dogs revealed similar changes for the dogs with IPF and chronic bronchitis, which suggested a common response to disease processes in otherwise different lung diseases. Specific biomarkers for IPF were not identified.

The extraosseal intrathoracic radiopaque bone cyst in West Highland White Terrier – a case report

The aim of this report was to present a clinical case and diagnostics of intrathoracic bone cyst as well as successful outcome of the surgical treatment in a male, 3-year-old West Highland White Terrier dog, weighing 6.9 kg. The dog was admitted in a very poor condition with clinical signs of severe dyspnoea that developed during about one month period of time before admission to our clinic. The dog underwent physical examination and further examinations including radiological examination which revealed a radiopaque mass formation in the cranial mediastinum. Ultrasonographic examination showed the presence of fluid; following thoracentesis revealed pseudochylous fluid. The bone cyst was surgically removed and more than 10 months after surgery the dog’s health was very good without any difficulties. Bone cysts in dogs are infrequent; this was the first case at our clinic and presented a successful treatment.

Gastric carcinoma associated with Menetrier's‐like disease in a West Highland white terrier

A seven-year-old West Highland white terrier was presented for chronic vomiting associated with mild regenerative anaemia and hypoalbuminaemia. Further examination showed a giant polypoid cerebriform mass located in the lesser curvature of the stomach. Partial gastrectomy was performed and histology was consistent with hypertrophic gastritis with typical features of Ménétrier's disease. Five years after surgery, the dog was re-examined for recurrence of vomiting episodes. Endoscopy showed ulceration of the lesser curvature of the stomach and histological analysis revealed a poorly differentiated superficial gastric carcinoma surrounded by hypertrophic gastritis. To the authors' knowledge, this is the second time that coexistence of these two types of lesions is reported, suggesting that recurrence of gastritis could be the starting point of the tumoural process.

Repairing nictitans gland prolapse in dogs

THE nictitans gland is responsible for about 40 per cent of the aqueous part of the precorneal tear film. Its prolapse is very commonly seen in veterinary ophthalmology and it...

Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.

Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT). Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.

Clinical conundrum

A 9-year-old West Highland White Terrier presented for a dental check having been diagnosed with diabetes a year before. He required extensive dental treatment including several extractions.

Hemolytic anemia caused by hereditary pyruvate kinase deficiency in a West Highland White Terrier dog

La deficiencia de piruvato quinasa (PK) es un desorden hemolitico autosomico recesivo descrito en perros y gatos. La piruvato quinasa es una de las enzimas regulatorias esenciales de la glicolisis anaerobica, la deficiencia de esta enzima causa una destruccion prematura de los eritrocitos. El presente es un estudio de caso y relata los hallazgos clinicos y paraclinicos en un perro brasileno de la raza West Highland White Terrier (WHWT) con historia de debilidad e intolerancia al ejercicio. El paciente presentaba mucosas palidas, anemia hemolitica bastante regenerativa y osteoclerosis. La deficiencia de PK fue confirmada a traves de una prueba de ADN raza especifica para la insercion 6bp en el extremo 3' del exon 10 de la secuencia del gen de la piruvato quinasa eritrocitaria (R-PK) como fue descrito. Al perro se le practico eutanasia a los 20 meses de edad debido al deterioro de su estado clinico, el cual incluyo anemia e incompatibilidad sanguinea. En otros casos descritos en perros de la raza WHWT con esta deficiencia, existen relatos hasta de nueve anos de sobrevivencia. Los defectos hereditarios deben ser objeto de diagnostico diferencial importante en casos de anemias hemoliticas cronicas en animales jovenes despues de la exclusion diagnostica de disturbios inmunomediados y causas infecciosas. Adicionalmente, perros de razas puras para las cuales la prueba de ADN esta disponible para enfermedades hereditarias deben ser evaluados antes de la edad reproductiva para limitar la diseminacion del alelo mutante y la generacion futura de animales deficientes.

Bilateral angular carpal deformity in a dog with craniomandibular osteopathy

A four-month-old West Highland White Terrier was presented to the Small Animal Teaching Hospital at the University of Liverpool with the complaint of a bilateral angular carpal deformity. A 20° valgus deformity was present in both thoracic limbs, centred on the distal radial physes. Both distal ulnas were grossly thickened and there was concomitant thickening of the rostral mandible and calvarium. The dog exhibited signs of resentment on palpation of the mandible and signs of pain were elicited on flexion and extension of both elbow joints. No signs of pain were evident on palpation of the ulnas or calvarium. Radiographic images of both ulnas showed marked amorphous periosteal new bone formation. The distal ulnar physes were closed centrally and both elbow joints had humeroulnar subluxation. Radiographic changes to the calvarium and mandibular rami were consistent with a diagnosis of craniomandibular osteopathy. A bilateral ulna ostectomy was performed to correct the angular limb deformity and elbow subluxations. Histology of the ostectomised pieces showed changes consistent with craniomandibular osteopathy.

PTPN22 polymorphisms may indicate a role for this gene in atopic dermatitis in West Highland white terriers

BackgroundCanine atopic dermatitis is an allergic inflammatory skin disease common in West Highland white terriers. A genome-wide association study for atopic dermatitis in a population of West Highland white terriers identified a 1.3 Mb area of association on CFA17 containing canine protein tyrosine phosphatase non-receptor type 22 (lymphoid) PTPN22. This gene is a potential candidate gene for canine atopic dermatitis as it encodes a lymphoid-specific signalling mediator that regulates T-cell and possibly B-cell activity.FindingsSequencing of PTPN22 in three atopic and three non-atopic West Highland white terriers identified 18 polymorphisms, including five genetic variants with a bioinformatically predicted functional effect. An intronic polymorphic repeat sequence variant was excluded as the cause of the genome-wide association study peak signal, by large-scale genotyping in 72 West Highland white terriers (gene-dropping simulation method, P = 0.01).ConclusionsThis study identified 18 genetic variants in PTPN22 that might be associated with atopic dermatitis in West Highland white terriers. This preliminary data may direct further study on the role of PTPN22 in this disease. Large scale genotyping and complementary genomic and proteomic assays would be required to assess this possibility.

Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study.

BackgroundCanine atopic dermatitis (AD) is a common inflammatory skin disease associated with defects in the epidermal barrier, particularly in West Highland white terriers (WHWTs). It shares many similarities with human AD, and so may be a useful animal model for this disease. Epidermal dysfunction in human AD can be caused by mutations in the gene encoding the epidermal protein filaggrin (FLG) and, in some atopic patients, be associated with altered FLG mRNA and protein expression in lesional and/or non-lesional skin. In experimental models of canine AD, mRNA expression of the orthologous canine filaggrin gene may be reduced in non-lesional skin compared with healthy controls. However, there is no published data on canine filaggrin mRNA expression in the skin of dogs with naturally-occurring AD. Hence, the aim of this pilot study was to develop a reverse transcriptase real-time PCR assay to compare filaggrin mRNA expression in the skin of atopic (n = 7) and non-atopic dogs (n = 5) from five breeds, including eight WHWTs.FindingsOverall, filaggrin mRNA expression in non-lesional atopic skin was decreased compared to non-lesional non-atopic skin (two fold change); however this difference was only statistically significant in the subgroup of WHWTs (P = 0.03).ConclusionsAlthough limited by the small sample size, these results indicate that, comparable to some cases of human AD, altered filaggrin mRNA expression may exist in the skin of some atopic dogs with naturally-occurring disease. Additional studies, including larger sample numbers, will be necessary to confirm this finding and to investigate whether mutations in the filaggrin gene exist and contribute to epidermal lesions of AD in dogs.

Unusual Systemic Metastases of Malignant Seminoma in a Dog

Unilateral enlargement of left testicle and scrotum was detected in an 8-year-old West Highland White Terrier. The histopathological diagnosis after surgery was a seminoma (SEM) tumour, and a diagnosis of metastatic foci was also detected in vaginal tunic and scrotum. Two months later, new metastatic SEM foci in the skin were diagnosed. Twenty-two months after the initial orchiectomy new multiple cutaneous nodules and a swelling of periesophageal structures were observed. Finally, the necropsy revealed multiple malignant metastatic SEM focus. To the author's knowledge, this is the first description of a canine SEM with unusual widespread metastasis on the base of tongue, soft palate, trachea and pericardium.