Phocine Distemper in German Seals, 2002

Approximately 21,700 seals died during a morbillivirus epidemic in northwestern Europe in 2002. Phocine distemper virus 1 was isolated from seals in German waters. The sequence of the P gene showed 97% identity with the Dutch virus isolated in 1988. There was 100% identity with the Dutch isolate from 2002 and a single nucleotide mismatch with the Danish isolate

Linkage mapping of ovine microphthalmia to chromosome 23, the sheep orthologue of human chromosome 18

PURPOSE: To characterize the phenotype and map the locus responsible for autosomal recessive inherited ovine microphthalmia (OMO) in sheep. METHODS: Microphthalmia-affected lambs and their available relatives were collected in a field, and experimental matings were performed to obtain affected and normal lambs for detailed necropsy and histologic examinations. The matings resulted in 18 sheep families with 48 cases of microphthalmia. A comparative candidate gene approach was used to map the disease locus within the sheep genome. Initially, 27 loci responsible for the microphthalmia-anophthalmia phenotypes in humans or mice were selected to test for comparative linkage. Fifty flanking markers that were predicted from comparative genomic analysis to be closely linked to these genes were tested for linkage to the disease locus. After observation of statistical evidence for linkage, a confirmatory fine mapping strategy was applied by further genotyping of 43 microsatellites. RESULTS: The clinical and pathologic examinations showed slightly variable expressivity of isolated bilateral microphthalmia. The anterior eye chamber was small or absent, and a white mass admixed with cystic spaces extended from the papilla to the anterior eye chamber, while no recognizable vitreous body or lens was found within the affected eyes. Significant linkage to a single candidate region was identified at sheep chromosome 23. Fine mapping and haplotype analysis assigned the candidate region to a critical interval of 12.4 cM. This ovine chromosome segment encompasses an ancestral chromosomal breakpoint corresponding to two orthologue segments of human chromosomes 18, short and long arms. For the examined animals, we excluded the complete coding region and adjacent intronic regions of ovine TGIF1 to harbor disease-causing mutations. CONCLUSIONS: This is the first genetic localization for hereditary ovine isolated microphthalmia. It seems unlikely that a mutation in the TGIF1 gene is responsible for this disorder. The studied sheep represent a valuable large animal model for similar human ocular phenotypes

A Duplication in the Canine β-Galactosidase Gene GLB1 Causes Exon Skipping and GM(1)-Gangliosidosis in Alaskan Huskies

GM(1)-gangliosidosis is a lysosomal storage disease that is inherited as an autosomal recessive disorder, predominantly caused by structural defects in the β-galactosidase gene (GLB1). The molecular cause of GM(1)-gangliosidosis in Alaskan huskies was investigated and a novel 19-bp duplication in exon 15 of the GLB1 gene was identified. The duplication comprised positions +1688–+1706 of the GLB1 cDNA. It partially disrupted a potential exon splicing enhancer (ESE), leading to exon skipping in a fraction of the transcripts. Thus, the mutation caused the expression of two different mRNAs from the mutant allele. One transcript contained the complete exon 15 with the 19-bp duplication, while the other transcript lacked exon 15. In the transcript containing exon 15 with the 19-bp duplication a premature termination codon (PTC) appeared, but due to its localization in the last exon of canine GLB1, nonsense-mediated RNA decay (NMD) did not occur. As a consequence of these molecular events two different truncated GLB1 proteins are predicted to be expressed from the mutant GLB1 allele. In heterozygous carrier animals the wild-type allele produces sufficient amounts of the active enzyme to prevent clinical signs of disease. In affected homozygous dogs no functional GLB1 is synthesized and G(M1)-gangliosidosis occurs

Interfollicular fibrosis in the thyroid of the harbour porpoise: An endocrine disruption?

Previous studies have described high levels of polychlorobiphenyls (PCB), polybrominated diphenylether (PBDE), toxaphene, ,p0-dichlorodiphenyltrichloroethane (DDT), and ,p0-dichlorodiphenyldichloroethylene (DDE) in the blubber of the harbour porpoise from the North Sea raising the question of a potential endocrine disruption in this species. In the present study, the thyroids of 57 harbour porpoises from the German and Danish (North and Baltic Seas), Norwegian, and Icelandic coasts have been collected for histological and immunohistological investigations. The number of follicles and the relative distribution of follicles, connective, and solid tissues (%) were quantified in the thyroid of each individual. Then, the potential relationship between the thyroid morphometry data and previously described organic compounds (namely, PCB, PBDE, toxaphene, DDT, and DDE) was investigated using factor analysis and multiple regressions. Thyroid morphology differed strongly between ampling sites. Porpoises from the German (North and Baltic Seas) and Norwegian coasts displayed a high percentage of connective tissues between 30 and 38% revealing severe interfollicular fibrosis and a high number of large follicles (diameter >200 lm). A correlation-based principal component analysis (PCA) revealed two principal components explaining 85.9% of the total variance. The variables PCB, PBDE, DDT, and DDE compounds loaded highest on PC1 whereas toxaphene compound loaded most on PC2. Our results pointed out a relationship between PC1 (PCBs, PBDE, DDE, and DDT compounds) and interfollicular fibrosis in the harbour porpoise thyroids. Such an association is not alone sufficient for a cause–effect relationship but supports the hypothesis of a contaminant-induced thyroid fibrosis in harbour porpoises raising the question of the longterm viability in highly polluted areas