RESUMEN
BACKGROUND: ICR-derived glomerulonephritis (ICGN) strain is a novel inbred strain of mice with a hereditary nephrotic syndrome. Deletion mutation of tensin 2 (Tns2), a focal adhesion molecule, has been suggested to be responsible for nephrotic syndrome in ICGN mice; however, the existence of other associative factors has been suggested. METHODS AND RESULTS: To identify additional associative factors and to better understand the onset mechanism of nephrotic syndrome in ICGN mice, we conducted a comprehensive gene expression analysis using DNA microarray. Immune-related pathways were markedly altered in ICGN mice kidney as compared with ICR mice. Furthermore, the gene expression level of complement component 1, s subcomponent (C1s), whose human homologue has been reported to associate with lupus nephritis, was markedly low in ICGN mouse kidney. Real-time quantitative reverse transcription-polymerase chain reaction confirmed a low expression level of C1s in ICGN mouse liver where the C1s protein is mainly synthesized. A high serum level of anti-dsDNA antibody and deposits of immune complexes were also detected in ICGN mice by enzyme-linked immunosorbent assay and immunohistochemical analyses, respectively. CONCLUSION: Our results suggest that the immune system, especially the complement system, is associated with nephrotic syndrome in ICGN mice. We identified a low expression level of C1s gene as an additional associative factor for nephrotic syndrome in ICGN mice. Further studies are needed to elucidate the role of the complement system in the onset of nephrotic syndrome in ICGN mice.
Asunto(s)
Complemento C1s/genética , Glomerulonefritis/genética , Síndrome Nefrótico/genética , Transcriptoma , Animales , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Complemento C1s/metabolismo , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Glomerulonefritis/sangre , Glomerulonefritis/inmunología , Humanos , Inmunohistoquímica , Riñón/metabolismo , Riñón/patología , Nefritis Lúpica/genética , Ratones , Ratones Endogámicos ICR , Síndrome Nefrótico/sangre , Síndrome Nefrótico/inmunología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: The a-wave of the photopic electroretinogram (ERG) of macaque monkeys is made up of the electrical activities of cone photoreceptors and post-photoreceptoral neurons. However, it is not known whether the contributions of these two components change in retinas with inherited photoreceptor degeneration. The purpose of this study was to determine the contributions of cones and post-photoreceptoral neurons to the a-wave of the photopic ERGs in rhodopsin Pro347Leu transgenic (Tg) rabbits. METHODS: Ten Tg and 10 wild-type (WT) New Zealand White rabbits were studied at 4 and 12 months of age. The a-waves of the photopic ERGs were elicited by xenon flashes of different stimulus strengths before and after the activities of post-photoreceptoral neurons were blocked by intravitreal injections of a combination of 0.2 to 0.4 mM of 6-cyano-7-nitrouinoxaline-2,3(1H,4H)-dione, disodium (CNQX) and 2 to 4 mM of (±)-2-amino-4-phosphonobutyric acid. RESULTS: The percentage contribution of the cone photoreceptors to the photopic ERG a-waves increased with increasing stimulus strength, and the percentage ranged from 54% to 75% in 4-month-old WT rabbits. In contrast, the percentage contribution of the cone photoreceptors in 4-month-old Tg rabbits ranged from 32% to 51% (P < 0.05). The mean percentage contribution of cone photoreceptors became still smaller at 11% to 48% in 12-month-old Tg rabbits. CONCLUSIONS: These results suggest that the relative contribution of cone photoreceptors to the photopic ERG a-wave is smaller in retinas with inherited photoreceptor degeneration. This indicates that the a-waves of the photopic ERGs in patients with retinitis pigmentosa must consider this lower contribution from the cone photoreceptors.