International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 150 - EXPRESSION AND FUNCTION OF BASP1: A COSUPPRESSOR OF THE WILMS’ TUMOUR SUPPRESSOR PROTEIN, WT1

Allsop JE 1, Moorwood K 1, Charalambous M 1, Lahiri D 1, Dutton JR 1, Roberts GE 2, Ward A 1

1 University of Bath, Bath, United Kingdom, 2 University of Manchester, Manchester, United Kingdom

The Wilms’ tumour suppressor protein, Wt1, is a transcriptional regulator that plays a key role in the development of several organ systems. Wt1 homozygous knock-out mice showed agenesis of the kidneys, gonad and spleen, and also abnormal development of the heart diaphragm and retinal ganglia. The transcriptional activation domain of Wt1 is subject to regulation by an N-terminal suppression domain. This transcriptional suppression domain has been proposed to function by recruiting a cosuppressor protein to Wt1 that can block the function of the transcriptional activation domain. Transfection assays have identified Brain acid-soluble protein (Basp1) as a component of the Wt1 cosuppressor that can regulate Wt1 transcriptional activity. Basp1 is a nuclear factor that associates with Wt1 in cells that naturally express both proteins. Analysis of embryonic and adult kidney sections reveals that Basp1 is present in the developing nephron structures of the embryonic kidney and that, coincident with Wt1, its expression is restricted to the highly specialized podocyte cells of the adult kidney. Basp1 however is also more widely expressed than Wt1, including within the CNS, heart, liver and tongue. We are developing a mouse knockout model to test whether Basp1 and Wt1 interact in vivo, and to ascertain the role Basp1 plays in development.

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