RESUMO
Congenital stationary night blindness (CSNB) is a non-progressive, clinically and genetically heterogeneous disease of impaired night vision. We report a naturally-occurring, stationary, autosomal recessive phenotype in beagle dogs with normal daylight vision but absent night vision. Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had "negative-type" mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans. Homozygosity mapping ruled out most known CSNB candidates as well as CACNA2D4 and GNB3. Three remaining genes were excluded based on sequencing the open reading frame and intron-exon boundaries (RHO, NYX), causal to a different form of CSNB (RHO) or X-chromosome (NYX, CACNA1F) location. Among the genes expressed in the photoreceptors and their synaptic terminals, and mGluR6 cascade and modulators, reduced expression of GNAT1, CACNA2D4 and NYX was observed by qRT-PCR in both carrier (n = 2) and affected (n = 2) retinas whereas CACNA1F was down-regulated only in the affecteds. Retinal morphology revealed normal cellular layers and structure, and electron microscopy showed normal rod spherules and synaptic ribbons. No difference from normal was observed by immunohistochemistry (IHC) for antibodies labeling rods, cones and their presynaptic terminals. None of the retinas showed any sign of stress. Selected proteins of mGluR6 cascade and its modulators were examined by IHC and showed that PKCα weakly labeled the rod bipolar somata in the affected, but intensely labeled axonal terminals that appeared thickened and irregular. Dendritic terminals of ON-bipolar cells showed increased Goα labeling. Both PKCα and Goα labeled the more prominent bipolar dendrites that extended into the OPL in affected but not normal retinas. Interestingly, RGS11 showed no labeling in the affected retina. Our results indicate involvement of a yet unknown gene in this canine model of complete CSNB.
Assuntos
Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/patologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Predisposição Genética para Doença/genética , Miopia/genética , Miopia/patologia , Cegueira Noturna/genética , Cegueira Noturna/patologia , Retina/fisiopatologia , Animais , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Modelos Animais de Doenças , Cães , Oftalmopatias Hereditárias/metabolismo , Oftalmopatias Hereditárias/fisiopatologia , Feminino , Regulação da Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Proteínas Heterotriméricas de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Humanos , Masculino , Miopia/metabolismo , Miopia/fisiopatologia , Cegueira Noturna/metabolismo , Cegueira Noturna/fisiopatologia , Linhagem , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/fisiologia , Proteoglicanas/genética , Proteoglicanas/metabolismo , Proteínas RGS/genética , Proteínas RGS/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/fisiologiaRESUMO
This study was conducted to investigate the effects of parity and litter size on gestation length in beagle bitches. The mean duration of the initial elevation (>2 ng/mL) in progesterone concentrations after the onset of proestrus was shorter (P < 0.05) in bitches without (nulliparous) whelping experience than in bitches with (multiparous) whelping experience (6.9 d versus 8.0 d). When calculated as the interval between the day of initial elevation in progesterone concentrations and the day of whelping, the gestation length in the nulliparous bitches was noted to be similar to that in the multiparous bitches (64.3 d versus 64.2 d). No significant correlation between gestation length and litter size was observed in any of the bitches. Our results indicate that the gestation length in beagle bitches is not affected by parity or litter size.
Assuntos
Cães/fisiologia , Tamanho da Ninhada de Vivíparos , Paridade , Gravidez/fisiologia , Animais , Feminino , Proestro , Progesterona/sangue , Fatores de TempoRESUMO
The aim of this study was to investigate differences between the progesterone profiles of Beagle bitches with (multiparous) and without (nulliparous) the whelping experience and to examine whether the selection of bitches by progesterone analyses before the programmed mating improved the whelping rates. In the first experiment, the progesterone profiles of nulliparous and multiparous bitches were evaluated from Days 1 to 13 (onset of prooestrus = Day 0). The mean duration of the elevation in progesterone levels (> 2 ng/mL) after the onset of prooestrus tended to be approximately 1 day shorter in nulliparous bitches (7.7 days) than in multiparous bitches (8.5 days). In the second experiment, progesterone analyses in the bitches were carried out once on Days 4, 5 or 6. Bitches with progesterone levels of > 10 ng/mL were excluded from mating because it was unclear when the progesterone levels reached > 10 ng/mL considering the optimal date for mating. No significant differences were observed in the percentages of bitches excluded from mating and in the whelping rates of the mated bitches between the groups, irrespective of the day of progesterone analysis and the type of bitch. In conclusion, the initial elevation of progesterone levels was of shorter duration in nulliparous bitches. The selection of bitches by the measurement of progesterone levels once before mating was not effective for the programmed mating.
