ABSTRACT
BACKGROUND: Investigations of rabid animals that cross provincial/territorial boundaries are resource intensive and complex because of their multi-jurisdictional and multi-sectoral nature. OBJECTIVE: To describe the multi-jurisdictional responses to two unrelated rabid puppies originating from Nunavut. METHODS: A descriptive summary of the investigations following the identification of a rabid puppy in Alberta (August 2013) and another in Saskatchewan (December 2014). RESULTS: These investigations involved public health and agriculture authorities in five provinces/territories, as well as the Canadian Food Inspection Agency (CFIA). In Alberta, a puppy who became ill after being transported by air from Nunavut was euthanized and diagnosed with rabies (Arctic fox variant). Eighteen individuals were assessed for exposure to rabies; nine received rabies post-exposure prophylaxis (RPEP). An exposed household dog that tested negative was electively euthanized. In Nunavut, the rabid puppy's mother and litter mates were placed under quarantine. In Saskatchewan, another puppy became ill during transit by air from Nunavut. It was subsequently euthanized and diagnosed with rabies (Arctic fox variant). Two of three Saskatchewan individuals, including a veterinary technician, received RPEP. Two Nova Scotia residents were exposed to the puppy while in Nunavut and received RPEP. One household dog received booster vaccination, was quarantined for 45 days and remained asymptomatic. In Nunavut, the rabid puppy's mother and litter mates were not identified. In both cases, exposure to an Arctic fox was the probable source of rabies in the puppies. CONCLUSION: Translocation of dogs from the north where Arctic fox rabies is endemic poses a risk to human and animal health and may negatively impact control of rabies in Canada. There is currently no national framework to prevent inter-jurisdictional movement of potentially rabid animals in Canada.
ABSTRACT
BACKGROUND: Mutations in CACNA1F, which encodes the Ca(v)1.4 subunit of a voltage-gated L-type calcium channel, cause X-linked incomplete congenital stationary night blindness (CSNB2), a condition of defective retinal neurotransmission which results in night blindness, reduced visual acuity, and diminished ERG b-wave. We have characterized two putative murine CSNB2 models: an engineered null-mutant, with a stop codon (G305X); and a spontaneous mutant with an ETn insertion in intron 2 of Cacna1f (nob2). METHODS: Cacna1f ( G305X ): Adults were characterized by visual function (photopic optokinetic response, OKR); gene expression (microarray) and by cell death (TUNEL) and synaptic development (TEM). Cacna1f ( nob2 ): Adults were characterized by properties of Cacna1f mRNA (cloning and sequencing) and expressed protein (immunoblotting, electrophysiology, filamin [cytoskeletal protein] binding), and OKR. RESULTS: The null mutation in Cacna1f ( G305X ) mice caused loss of cone cell ribbons, failure of OPL synaptogenesis, ERG b-wave and absence of OKR. In Cacna1f ( nob2 ) mice alternative ETn splicing produced ~90% Cacna1f mRNA having a stop codon, but ~10% mRNA encoding a complete polypeptide. Cacna1f ( nob2 ) mice had normal OKR, and alternatively-spliced complete protein had WT channel properties, but alternative ETn splicing abolished N-terminal protein binding to filamin. CONCLUSIONS: Ca(v)1.4 plays a key role in photoreceptor synaptogenesis and synaptic function in mouse retina. Cacna1f ( G305X ) is a true knockout model for human CSNB2, with prominent defects in cone and rod function. Cacna1f ( nob2 ) is an incomplete knockout model for CSNB2, because alternative splicing in an ETn element leads to some full-length Ca(v)1.4 protein, and some cones surviving to drive photopic visual responses.
