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An 8-year-old, female spayed Domestic Shorthair cat was presented to the Auburn University Emergency and Critical Care service for evaluation of pleural effusion and a suspected intrathoracic mass. Computed tomography was performed which confirmed the presence of a large intrathoracic mass, likely heart-based. Fine-needle aspirates were obtained and a cytologic diagnosis of a neuroendocrine tumor was made. Treatment with toceranib phosphate was briefly attempted at home by the owners. The cat died at home approximately 6 weeks after diagnosis. Necropsy and subsequent histopathologic examination revealed a metastatic neuroendocrine carcinoma of aortic body origin. Aortic body tumors are extremely rare in cats and to the authors' knowledge, a neuroendocrine carcinoma of aortic body origin with distant metastases has not yet been reported in a cat., (© 2016 American Society for Veterinary Clinical Pathology.)

Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15). Notably, previous studies of a Pea15 targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role for PEA15 in development of a complex cerebral cortex that is only apparent in gyrencephalic species. [ABSTRACT FROM AUTHOR]