Background Canine (Canis lupus familiaris) atopic dermatitis (AD) shares similar clinical signs to human AD. The abnormal immune response of AD is orchestrated by T lymphocytes, and may include variable involvement of cytokines, regulatory T (Treg) cells, eosinophils, mast cells and other immune components. Helper T (Th)2 cytokines often predominate initially, followed by Th1 cytokines in more chronic phases. Hypothesis/Objectives Pro-inflammatory and Treg cytokines have been shown to play a role in human AD, yet their importance is not clear in canine AD. Hence, this study aimed to measure the concentrations of cytokines/chemokines not traditionally associated with Th1/Th2 response. Animals Canine AD patients (n = 27), compared to control dogs (n = 11). Methods and materials A total of 19 plasma cytokines were assayed using canine specific multiplex immuno-assays. Results The plasma concentrations of CXC Motif Chemokine Ligand 8 (CXCL8), interleukin (IL)-7 and IL-15 cytokines were elevated in canine AD patients, compared to control dogs. In addition, stem-cell factor (SCF) concentrations were reduced in the plasma of canine AD patients compared to control dogs. Distinct cytokine profiles were found in dogs belonging to the Staffordshire breeds, a group with increased risk of AD. In particular, granulocyte-macrophage colony-stimulating factor (GM-CSF) had significantly elevated concentrations. Conclusions and clinical relevance Some of the plasma cytokine alterations in canine AD described here, particularly of IL-7, have not been reported previously. Monitoring these distinctive cytokine alterations could be useful for diagnosis and monitoring of canine AD in dogs.

Developmental anomalies are an important cause of stillbirth and early perinatal death in companion animals. Many of these disorders remain poorly understood and provide an opportunity as a spontaneous animal model for human disease. Pentalogy of Cantrell is a rare congenital syndrome described in human neonates. It is a ventral midline closure defect with a proposed familial inheritance in humans. This syndrome involves five defects, including the thoracoabdominal wall, sternal, diaphragmatic, pericardial and cardiac malformations. Diverse expressions of these defects have been described in humans and sporadically in domestic animals. This severe syndrome commonly harbors a poor prognosis, posing an ethical and surgical dilemma. To better understand this syndrome and its presentation in dogs, we describe two rare cases of Pentalogy of Cantrell in a litter of papillon dogs. The affected puppies had anomalies compatible with the Pentalogy of Cantrell, including thoracoabdominal schisis, ectopia cordis, sternal cleft, pericardial agenesis, and diaphragmatic defects. The diagnosis was confirmed by advanced imaging (computed tomography) and postmortem examinations. The family history of this litter was explored and other cases in domestic animals were reviewed. This is the first report of the complete Pentalogy of Cantrell with ectopia cordis in the dog and the only report on papillons. Similar to human cases, possible familial inheritance and suspected male gender bias were observed. Further research on this novel animal model, its pathogenesis and its hereditary basis, may be helpful in better understanding this rare developmental disorder.

Mucolipidosis II (ML II; I-cell disease) is caused by a deficiency of N-acetylglucosamine-1-phosphotransferase (GNPTAB; EC 2.7.8.17), which leads to a failure to internalize acid hydrolases into lysosomes for proper catabolism of various substances. This is an autosomal recessive lysosomal storage disease and causes severe progressive neuropathy and oculoskeletal dysfunction in humans (OMIM 252500). A naturally occurring disease model has been reported in juvenile domestic cats (OMIA 001248–9685) with clinical signs similar to human patients. We investigated the molecular genetic basis of ML II in a colony of affected cats by sequencing the coding and regulatory regions of GNPTAB from affected and clinically healthy related and unrelated domestic cats and compared the sequences to the published feline genome sequence (NCBI-RefSeq accession no. XM_003989173.4, Gene ID: 101100231). All affected cats were homozygous for a single base substitution (c.2644C > T) in exon 13 of GNPTAB. This variant results in a premature stop codon (p.Gln882*) which predicts severe truncation and complete dysfunction of the GNPTAB enzyme. About 140 GNPTAB variants have been described in human ML II patients, with 41.3% nonsense/missense mutations, nine occurring in the same gene region as in this feline model. Restriction fragment length polymorphism and allelic discrimination real-time polymerase chain reaction assays accurately differentiated between clear, asymptomatic carriers and homozygous affected cats. Molecular genetic characterization advances this large animal model of ML II for use to further define the pathophysiology of the disease and evaluate novel therapeutic approaches for this fatal lysosomal storage disease in humans.

Chronic superficial keratitis (CSK) is a progressive inflammatory condition of the eye (cornea) that can cause discomfort and blindness. Differential disease risk across dog breeds strongly suggests that CSK has a genetic basis. In addition to genetic risk, the occurrence of CSK is exacerbated by exposure to ultraviolet light. Genome-wide association analysis considered 109 greyhounds, 70 with CSK and the remainder with normal phenotype at an age over four years. Three co-located variants on CFA18 near the 5′ region of the Epidermal Growth Factor Receptor (EGFR) gene were associated with genome-wide significance after multiple-test correction (BICF2P579527, CFA18: 6,068,508, p_raw = 1.77 × 10⁻⁷, p_genome = 0.017; BICF2P1310662, CFA18: 6,077,388, p_raw = 4.09 × 10⁻⁷, p_genome = 0.040; BICF2P160719, CFA18: 6,087,347, p_raw = 4.09 × 10⁻⁷, p_genome = 0.040) (canFam4)). Of the top 10 associated markers, eight were co-located with the significantly associated markers on CFA18. The associated haplotype on CFA18 is protective for the CSK condition. EGFR is known to play a role in corneal healing, where it initiates differentiation and proliferation of epithelial cells that in turn signal the involvement of stromal keratocytes to commence apoptosis. Further validation of the putative functional variants is required prior to their use in genetic testing for breeding programs.