Transcriptomic analysis reveals a critical role for activating Gα mutations in spontaneous feline hyperthyroidism.

Feline hyperthyroidism (FHT) is a debilitating disease affecting > 10% of elderly cats. It is generally characterised by chronic elevation of thyroid hormone in the absence of circulating TSH. Understanding of the molecular pathogenesis of FHT is currently limited.

Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.

Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion. In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D), which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D.

Characterization of canine intestinal microRNA expression in inflammatory bowel disease and T-cell lymphoma.

Differentiating between canine inflammatory bowel disease (IBD) and intestinal T-cell lymphoma by histopathological examination of endoscopically-derived intestinal biopsies can be challenging and involves an invasive procedure requiring specialized equipment and training. A rapid, non-invasive method of diagnosis, such as blood or faecal analysis for a conserved and stable biomarker, would be a useful adjunct or replacement. Studies on dogs and humans with various types of lymphoma have shown altered microRNA (miRNA) expression patterns in blood, faeces and tissues indicating their potential use as biomarkers of disease.

Risk factors for upper urinary tract uroliths and ureteral obstruction in cats under referral veterinary care in the United Kingdom.

Background: Cats presenting with upper urinary tract uroliths (UUTUs) and ureteral obstruction ("obstructive UUTU") are typically younger than cats with idiopathic CKD that often have incidental nephroliths.

Hypothesis: Cats with upper urinary tract urolith have 2 clinical phenotypes; a more aggressive phenotype at risk of obstructive UUTU at a young age and a more benign phenotype in older cats, with reduced risk of obstructive UUTU.

Objectives: Identify risk factors for UUTU and for obstructive UUTU.

Etiology and Pathophysiology of Diabetes Mellitus in Dogs.

Canine diabetes results from a wide spectrum of clinical pathophysiological processes that cause a similar set of clinical signs. Various causes of insulin deficiency and beta cell loss, insulin resistance, or both characterize the disease, with genetics and environment playing a role. Understanding the genetic and molecular causes of beta cell loss will provide future opportunities for precision medicine, both from a therapeutic and preventative perspective.

Genetics of canine diabetes mellitus part 2: Current understanding and future directions.

Part 1 of this 2-part review outlined the importance of disease classification in diabetes genetic studies, as well as the ways in which genetic variants may contribute to risk of a complex disease within an individual, or within a particular group of individuals. Part 2, presented here, describes in more detail our current understanding of the genetics of canine diabetes mellitus compared to our knowledge of the human disease. Ongoing work to improve our knowledge, using new technologies, is also introduced.

Long-term effect of neutering on plasma luteinising hormone concentration in cats.

Objectives: The objectives of this study were to validate a commercially available luteinising hormone (LH) cat ELISA, to determine whether the increases in plasma LH concentration that occur after neutering are maintained throughout cats' lives and if other factors such as calendar seasons in both intact and neutered cats, and neutering age in neutered cats, influence plasma LH concentrations.

Methods: Stored plasma samples from client-owned cats were used for the measurement of LH concentrations. Clinical data, including age, sex, age at neutering and medical history, were reviewed.

Activation of the Immune-Metabolic Receptor GPR84 Enhances Inflammation and Phagocytosis in Macrophages.

GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. GPR84 activation is involved in the inflammatory response, but the mechanisms by which it modulates inflammation have been incompletely described. In this study, we investigated GPR84 expression, activation, and function in macrophages to establish the role of the receptor during the inflammatory response.

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease.

Research opens more doors.

Having gained some clinical experience before pursuing a research career, Lucy Davison is now seeking the best of both worlds as a clinician scientist.

Breed-specific hematological phenotypes in the dog: a natural resource for the genetic dissection of hematological parameters in a mammalian species.

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval.

Proteome-wide analysis of disease-associated SNPs that show allele-specific transcription factor binding.

A causative role for single nucleotide polymorphisms (SNPs) in many genetic disorders has become evident through numerous genome-wide association studies. However, identification of these common causal variants and the molecular mechanisms underlying these associations remains a major challenge. Differential transcription factor binding at a SNP resulting in altered gene expression is one possible mechanism.

Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene.

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI.

An allele of IKZF1 (Ikaros) conferring susceptibility to childhood acute lymphoblastic leukemia protects against type 1 diabetes.

Objective: IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3'-UTR of IKZF1 with C-ALL susceptibility, we tested whether IKZF1 is associated with the autoimmune disease type 1 diabetes.

Research Design And Methods: rs10272724 (T>C) near IKZF1 at 7p12 was genotyped in 8,333 individuals with type 1 diabetes, 9,947 control subjects, and 3,997 families of European ancestry.