Patent ID: 7166763
Filing Date: 2007-01-23
Classification: A01K,C12N,C12Q,G01N

Abstract:
1. A method of producing a mouse model of myxomatous valvular disease comprising the steps of: a) introducing a transgene containing 3-O-sulfotransferase-1nucleic acid sequences that flank a selectable marker gene into a mouse embryonic stem cell, wherein the transgene integrates into the genome of the mouse embryonic stem cell and the selectable marker gene disrupts the endogenous 3-O-sulfotransferase-1 gene, thereby producing a mouse embryonic stem cell wherein the endogenous 3-O-sulfotransferase-1 gene has been disrupted; b) introducing the mouse embryonic stem cell wherein the endogenous 3-O-sulfotransferase-1 gene has been disrupted, into a mouse embryo; c) implanting the resulting mouse embryo comprising the mouse ES cell of (b), into the uterus of a pseudopregnant mouse, wherein the pseudopregnant mouse gives birth to a chimeric mouse; d) breeding the chimeric mouse to produce a mouse heterozygous for a disruption in the 3-O-sulfotransferase-1 gene; e) backcrossing the heterozygous mouse for at least 10 backcrosses to produce a mouse that is heterozygous for the disrupted 3-O-sulfotransferase1 gene; and f) crossing a first mouse obtained in step (e) with a second mouse obtained in step (e) to produce a homozygous knock-out mouse lacking heparan sulfate 3-O-sulfotransferase-1 activity and exhibiting mitral valve degeneration, indicative of myxomatous valvular disease.