Variation in MUTYH expression in Arabian horses with Cerebellar Abiotrophy.

Cerebellar Abiotrophy (CA) is a neurodegenerative disease in Arabian horses affecting the cerebellum, more specifically the Purkinje neurons. Although CA occurs in several domestic species, CA in Arabian horses is unique in that a single nucleotide polymorphism (SNP) has been associated with the disease. Total RNA sequencing (RNA-seq) was performed on CA-affected horses to address the molecular mechanism underlying the disease. This research expands upon the RNA-seq work by measuring the impact of the CA-associated SNP on the candidate gene MutY homolog (MUTYH) and its regulation, isoform-specific expression and protein localization. We hypothesized that the CA-associated SNP compromises the promoter region of MUTYH, leading to differential expression of its isoforms. Our research demonstrates that the CA-associated SNP introduces a new binding site for a novel transcription factor (Myelin Transcription Factor-1 Like protein, MYT1L). In addition, CA-affected horses show differential expression of a specific isoform of MUTYH as well as different localization in the Purkinje and granular neurons of the cerebellum.

Evaluation of P16 expression in canine appendicular osteosarcoma.

BACKGROUND: Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. RESULTS: We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. CONCLUSIONS: The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study.

Exposure to raccoon polyomavirus (RacPyV) in free-ranging North American raccoons (Procyon lotor).

There is evidence that raccoon polyomavirus is causative for neuroglial brain tumors in the western United States. It is unknown if infection is limited to geographic locales where tumors have been reported or is widespread, like human polyomaviruses. We demonstrate raccoons in western, eastern and midwestern states have been exposed to RacPyV by detection of antibodies to capsid protein, VP1. While raccoons in eastern and midwestern states are seropositive, exposure is lower than in the western states. Additionally, across geographic areas seropositivity is higher in older as compared to younger raccoons, similar to polyomavirus exposure in humans. Serum titers are significantly higher in raccoons with tumors compared to raccoons without. Unlike polyomavirus-associated diseases in humans, we did not detect significant sequence variation between tumor and non-tumor tissue in raccoons with tumors compared to those without tumors. This warrants further investigation into co-morbid diseases or genetic susceptibility studies of the host.

Characterization of the temporomandibular joint of the harbour porpoise (Phocoena phocoena) and Risso's dolphin (Grampus griseus).

OBJECTIVES: The temporomandibular joint (TMJ) in cetaceans is largely uncharacterized. This study aims to describe the macroscopic, microscopic, biochemical and biomechanical features of the TMJ of two species of the suborder Odontoceti: the harbour porpoise (Phocoena phocoena) and Risso's dolphin (Grampus griseus). Furthermore, we aim to elucidate the structure-function relationship of their TMJs and their possible role in echolocation. DESIGN: The TMJs from fresh cadaver heads of harbour porpoise (n=4) and Risso's dolphin (n=2) acquired from stranding were examined. Following macroscopical evaluation, the TMJs were investigated for their histological, mechanical and biochemical properties. RESULTS: The TMJs of the studied odontocetes were found to be fundamentally different from other mammals. Macroscopically, the TMJ lacks the typical joint cavity found in most mammals and is essentially a syndesmosis. Histological and microstructural analysis revealed that the TMJ discs were composed of haphazardly intersecting fibrous-connective tissue bundles separated by adipose tissue globules and various calibre blood vessels and nerve fibres. The collagen fibre composition was primarily collagen type I with lesser amounts of collagen type II. Sulphated glycosaminoglycan (sGAG) content was lower compared to other studied mammals. Finally, mechanical testing demonstrated the disc was stronger and stiffer in the dorsoventral direction than in the mediolateral direction. CONCLUSION: The spatial position of the TMJ, the absence of an articulating synovial joint, and the properties of the TMJ discs all reflect the unique suction-feeding mechanism adopted by the harbour porpoise and Risso's dolphin for underwater foraging. In addition, the presence of unique adipose globules, blood vessels and nerves throughout the discs may indicate a functional need beyond food apprehension. Instead, the disc may play a role in neurological sensory functions such as echolocation.