ABSTRACT
Rationale: Mutations in Transient Receptor Potential Channel 6 (TRPC6) gene are associated with autosomal dominant focal and segmental glomerulosclerosis (FSGS). The majority of the identified mutations affect the ion channel function. Since calcium channels are promising candidate drug targets, there is an an urgent need for a mouse model to assess new therapeutic drugs and to help delineate the pathogenic process leading to FSGS. We have previously reported the generation of three independent transgenic mouse lines carrying different Trpc6 mutations that display a glomerular disease comparable to the phenotype presented by individuals with FSGS. However, the utility of these models for drug testing is dampened by the late-onset of the presentation and the mild phenotypic manifestations. Methodology: In order to obtain a time-effective mouse model for Trpc6-associated FSGS we generated a new transgenic mutant Trpc6 mouse model emulating the amino acid change carried by the first pediatric patient of FSGS associated with a TRPC6 mutation: M132T. Results: Mice carrying the orthologous Trpc6 M131T transgene showed early onset proteinuria and early signs of FSGS. When exploring molecular consequences of the overexpression of this mutated form of Trpc6 in podocytes, differences in expression levels of Axin2 and β-catenin were found in glomeruli from transgenic Trpc6 M131T mice. These data supports the proposed molecular mechanisms related to the activation of calcineurin-NFAT/Wnt signaling, as outcome of the increased calcium influx caused by the mutated form of Trpc6. Conclusion: Given that the Trpc6 M131T mouse develops an early onset of FSGS-like phenotypes it represents a promising model for studying the pathogenesis of FSGS caused by TRPC6, facilitating the assessment of new drugs as treatments and allowing further studies to understand underlying molecular pathways involved in the development of the TRPC6 mediated disease.
ABSTRACT
A study conducted over a period of two years in a Western Serbian valley included in situ identification of autochthonous plum cultivars. Observation and recording of their phenological and pomological traits were performed using IBPGR and UPOV methodologies. Fifteen cultivars derived from Prunus domestica L. and two cultivars derived from P. insititia L. were identified. Flowering started between 24 March and 7 April and fruit ripening between 12 July (Petrovača) and 16 September (Trnovača). Fruit weight ranged from 6.79± 0.018 to 36.62± 0.251 g and stone weight from 0.14± 0.002 to 1.95± 0.023 g. The cultivars were classified as being extremely small in terms of fruit size. Rounded fruit shape and light-yellow ground colour were dominant. Skin colour ranged from amber to black. Yellow green was a dominant flesh colour and medium flesh firmness predominated. The fruits of the above cultivars could be processed, particularly into plum brandy, or they could be used fresh or dried. The selected plum cultivars can be used both in breeding programmes and as rootstocks as well as in further disease-related systematic studies under field and laboratory conditions.