Dr Daniel Gitterman

Staff Scientist


This person is a member of Sanger Institute Alumni.

My project aims to create a mouse model of rare and poorly understood kidney disorders. The model is generated using molecular biological techniques in embryonic stem cells to remove the mouse genes and replace them with the human ortholog.

A component of the immune system called Complement Factor H and its five related proteins (CFHR1 – CFHR5) have been found to play a key role in the pathology of several renal diseases which are poorly understood. By humanising the mouse locus containing these genes we hope to create a mouse model of the human pathology. One goal will be to investigate the utility of therapeutically targeting these proteins in the treatment of diseases such as atypical haemolytic uraemic syndrome (aHUS) and dense deposit disease (DDD).
The process of engineering mouse embryonic stem cells to contain the human rather than the mouse CFH locus relies on a number of genome engineering technologies. CRISPR/Cas9 is used for all steps targeting exogenous DNA sequences to specific positions in the mouse genome, which is required for excision of the mouse genes and preparation of the site for integration of the human genes. Sequential recombinase mediated cassette exchange is then used to insert human sequence in a step-wise fashion, gradually building up the human locus.

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