SULPHATE TRANSPORTER · Study of the sulphate exchanger Tat1 (SLC26A8) in spermatogenesis : analysis of its physiological role in mouse male germ cells and genetic investigation in the aetiology of human infertility
6РП — Действия „Мария Кюри“
- Период
- 2005-05-15 → 2006-05-14
- Финансиране от ЕС
- 40 000 €
- Участници
- 1
- Схема
- ERG
Линиите свързват координатора с партньорите.
Накратко на български
Белъкът Tat1 (транспортер на сулфати) се изследва в мъжките полови клетки, като при мишки без него сперматозоидите не се движат. Разбирането на тази функция помага при диагностиката на мъжко безплодие и търсенето на нови методи за контрацепция.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - SULPHATE TRANSPORTER (Study of the sulphate exchanger Tat1 (SLC26A8) in spermatogenesis: ... and genetic investigation in the aetiology of human infertility)
Tat1 (Slc26A8) is an anion transporter belonging to the solute carrier 26 (SLC26) family and exclusively expressed, in the adult testis, in cells undergoing spermatogenesis. We characterised a mutant mouse model which was deleted for Tat1 gene and observed that homozygous mutant males were sterile due to defects in sperm morphology and total lack of sperm motility. These results indicated that Tat1 was a critical factor for male fertility, therefore we decided to investigate Tat1 implication in human male infertility. We analysed sperm preparations from a cohort of patients showing defects in sperm motility, i.e. asthenozoospermia, and found a case with an absence of Tat1 expression in the sperm of the patient, suggesting that Tat1 gene could be implicated. By the time of the project completion, we were confirming this result via an analysis of the Tat1 gene sequence in this patient and we were also searching for mutations. Finally, we initiated a programme in order to identify possible inhibitors of Tat1 anion transport activity. This should provide useful tools for further studies of Tat1 function and would also serve as a basis for the development of potential molecules for male contraception.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Tat1 (SLC26A8) encodes for an anionic exchanger exclusively expressed at the plasma membrane of human adult germ cells undergoing spermatogenesis. Although so far the physiological role of this molecule is unknown, it has been shown to transport sulphate i n a chloride dependant manner and it is likely to fulfil critical functions during spermatogenesis. Indeed, Tat1 belongs to a family of transporters, which physiological importance has been clearly demonstrated by association with several human disorders ( Pendred syndrome, Dyastrophic dysplasia, Congenital chloride diarrhoea). Furthermore, Tat1 regulate the transport of sulphate that we know is essential for many biological processes (i.e growth, development). For instance, hyposulphation of the proteoglycans located in the extra-cellular matrix of the cartilage, leads to dramatic bone development defects in patients diagnosed for Dyastrophic dysplasia. In order to define the physiological function of Tat1 we propose to use an RNAi based methodology to specifically down-regulate Tat1 expression in the adult mouse testis. We will take advantage of a new expression vector designed to produce siRNA-like transcripts that can specifically initiate degradation of the endogenous mRNA to which they are homologous. We propose to generate transgenic mice with constructs producing Tat1 siRNA molecules, and therefore down-regulate Tat1 expression in the appropriated tissues (so far Tat1 has been shown to be solely expressed in the adult testis). In parallel, we will elect roporate the expression vector into adult mouse testis in order to locally inhibit Tat1 expression. Combination of these two approaches should allow characterisation of the potential spermatogenesis defects associated with the lack of Tat1 activity. Subsequent search for similar abnormalities in human infertile patients will permit to investigate Tat1 implication in the aetiology of this disorder.
Оригинален текст от CORDIS (на английски).
Участници
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISКоординаторФранция
Връзки
Данни: CORDIS, © Европейски съюз