The X-linked mouse mutation Bent tail is associated with a deletion of the Zic3 locus

Bent tail (BN:) is a spontaneous, semi-dominant mutation on the mouse X chromosome 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, unrelated to the BN: mutation, was also identified in the background strain. Refined genetic and physical mapping of the BN: critical region demonstrate that the mutation is associated with a <170 kb submicroscopic deletion that includes the anonymous microsatellite marker DXMit208 as well as the entire Zic3 locus. Human mutations in ZIC3 are associated with left-right axis malformations (MIM 306955, 208530, 207100). Abnormalities of abdominal and thoracic 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 deletion of Zic3 in BN: mice support a key role for this gene in neural tube development and closure.