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.
Carrel
T
T
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Purandare
S M
SM
Harrison
W
W
Elder
F
F
Fox
T
T
Casey
B
B
Herman
G E
GE
D000818:Animals; D015139:Blotting, Southern; D003433:Crosses, Genetic; D005260:Female; D017353:Gene Deletion; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009436:Neural Tube Defects / Q000235:genetics*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D012729:Sex Chromosome Aberrations; D013623:Tail / Q000002:abnormalities*; D014157:Transcription Factors / Q000235:genetics*; D014781:Viscera / Q000002:abnormalities; D014960:X Chromosome / Q000235:genetics*
D018398:Homeodomain Proteins; D014157:Transcription Factors; C491594:Zic3 protein, mouse