The X-linked mouse mutation Bent tail is associated with a deletion of theZic3 locus

Bent tail (Bn) is a spontaneous, semi-dominant mutation on the mouse X chro mosome that produces tail deformities and, rarely, open neural tube defects . Analysis of 292 normal male and affected male and female progeny from an intraspecific back-cross involving Bn supports a gene order of cen-DXMit89- 18.5 +/- 2.3 cM-DXMit166-1.4 +/- 0.7 cM-Bn-1.0 +/- 0.6 cM-DXMit140-4.8 +/- 1.3 cM-DXBay6-tel. A high frequency of sex chromosomal non-disjunction, unr elated to the Bn mutation, was also identified in the background strain. Re fined genetic and physical mapping of the Bn critical region demonstrate th at the mutation is associated with a <170 kb submicroscopic deletion that i ncludes the anonymous microsatellite marker DXMit208 as well as the entire Zic3 locus. Human mutations in ZIC3 are associated with left-right axis mal formations (MIM 306955, 208530, 207100). Abnormalities of abdominal and tho racic situs were also detected in viable Bn males and females. The presence of anal and spinal abnormalities in some of the human patients and the del etion of Zic3 in Bn mice support a key role for this gene in neural tube de velopment and closure.