Project description:Understanding altered expression of proteins and transcripts associated with Toxoplasma gondii infection in cats may improve our understanding of how this parasite manipulates the molecular microenvironment of the definitive host. We performed proteomics analysis of six organs (brain, heart, spleen, liver, lung and small intestine) in cats acutely infected with T. gondii. A total of 32,657 proteins were identified among the six examined organs, including 2,556 differentially expressed proteins (DEPs), of which 1,325 DEPs were up-regulated and 1,231 DEPs were down-regulated. The brain, liver, lung, spleen, heart and small intestine exhibited 125 DEPs, 463 DEPs, 255 DEPs, 283 DEPs, 855 DEPs and 675 DEPs, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on all proteins and DEPs in all organs, showed that many proteins were enriched in binding, cell part, cell growth and death, signal transduction, translation, sorting and degradation and immune system. Correlation between proteins and transcripts with differential expression patterns were detected in the heart (n = 9), liver (n = 19), lung (n = 9), small intestine (n = 17), and spleen (n = 3). These DEPs were mainly involved in immune response, tryptophan catabolism, and extracellular matrix remodeling. Future investigations are needed to identify the pathophysiological mechanisms underlying the reported associations between the identified proteins and transcripts and T. gondii infection.
Project description:The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linage was established on cat chromosome B3 (LOD 18.38, q = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG, identifying a valuable animal model for primary glaucoma that closely resembles the human disease providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies.