MKLN1 splicing defect in dogs with lethal acrodermatitis

Lethal acrodermatitis (LAD) is a genodermatosis with monogenic autosomal recessive inheritance in Bull Terriers and Miniature Bull Terriers. The LAD phenotype is characterized by poor growth, immune deficiency, and skin lesions, especially at the paws. Utilizing a combination of genome wide association study and haplotype analysis, we mapped the LAD locus to a critical interval of similar to 1.11 Mb on chromosome 14. Whole genome sequencing of an LAD affected dog revealed a splice region variant in the MKLN1 gene that was not present in 191 control genomes (chr14:5,731,405T>G or MKLN/:c.400+3A>C). This variant showed perfect association in a larger combined Bull Terrier/Miniature Bull Terrier cohort of 46 cases and 294 controls. The variant was absent from 462 genetically diverse control dogs of 62 other dog breeds. RT-PCR analysis of skin RNA from an affected and a control dog demonstrated skipping of exon 4 in the MKLN1 transcripts of the LAD affected dog, which leads to a shift in the MKLN1 reading frame. MKLN1 encodes the widely expressed intracellular protein muskelin 1, for which diverse functions in cell adhesion, morphology, spreading, and intracellular transport processes are discussed. While the pathogenesis of LAD remains unclear, our data facilitate genetic testing of Bull Terriers and Miniature Bull Terriers to prevent the unintentional production of LAD affected dogs. This study may provide a starting point to further clarify the elusive physiological role of muskelin 1 in vivo.Peer reviewe

Thrombopathies causing bleeding in a boxer and mixed-breed dog

Hereditary platelet function disorders are clinically characterized by recurrent surface bleeding and prolonged bleeding time, despite normal platelet count and coagulation tests. The authors describe persistent thrombopathies in two young dogs with increased bleeding tendencies but with normal plasma coagulation times and von Willebrand factor (vWf) concentrations. Buccal mucosal bleeding times were prolonged in both dogs. In aggregation studies, platelets underwent only a shape change or minimal aggregation in response to adenosine diphosphate and collagen. Whole-platelet adenine nucleotide concentrations were normal. Electron microscopic evaluation of fibrinogen and vWf binding to the platelets of case no. 1 demonstrated the presence of glycoprotein IIb/IIIa and Ib receptors. Thus, the intrinsic platelet function defects may be different in these two dogs and may likely represent secretion/signal transduction disorders.</jats:p

Radiographic and computed tomographic evaluation and gait analysis of Brazilian minipigs with syndactyly

OBJECTIVE To characterize a population of Brazilian minipigs with naturally occur­ring syndactyly by use of plain radiographs and CT images and to evalu­ate kinetic and temporospatial variables by use of a pressure-sensing walkway. ANIMALS 10 Brazilian minipigs from 6 to 8 months of age (group 1, 5 healthy pigs [body weight, 10.5 to 18.5 kg]; group 2, 5 pigs with syndactyly [body weight, 7.5 to 18.0 kg]). PROCEDURES Forelimbs and hind limbs of all pigs were assessed by use of radiography and CT. Gait was analyzed by use of a pressure-sensing walkway. RESULTS All limbs of all pigs of group 2 had syndactyly. Two forelimbs had complex-1 syndactyly, and 8 forelimbs had complex-2 syndactyly. Four hind limbs had simple syndactyly, 1 hind limb had complex-1 syndactyly, and 5 hind limbs had complex-2 syndactyly. Kinetic and temporospatial values and symmetry indices did not differ between groups. Plantar and pal­mar surfaces of healthy pigs had 2 areas of maximum pressure, whereas plantar and palmar surfaces of pigs with syndactyly had only 1 area of maximum pressure. CONCLUSIONS AND CLINICAL RELEVANCE In this population of pigs, the most common type of syndactyly was com­plex-2, and comparison with the healthy group revealed no alteration in kinetic and temporospatial variables. Therefore, results suggested that syndactyly in young minipigs did not cause locomotor disturbances.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science Universidade Estadual Paulista (UNESP)Department of Animal Reproduction and Veterinary Radiology School of Veterinary Medicine and Animal Science Universidade Estadual Paulista (UNESP)Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science Universidade Estadual Paulista (UNESP)Department of Animal Reproduction and Veterinary Radiology School of Veterinary Medicine and Animal Science Universidade Estadual Paulista (UNESP)FAPESP: 2009/18299-7CNPq: 300710/2013-