Complementation Mapping of Skeletal and Central Nervous System Abnormalities in Mice of the piebald Deletion Complex

The s^15DttMb, s^36Pub, s^1Acrg and s^24Pub piebald deletion alleles belong to a set of overlapping deficiencies on the distal portion of chromosome 14. Molecular analysis was used to define the extent of the deletions. Mice homozygous for the smallest deletion, s^15DttMb, die shortly after delivery and display alterations in the central nervous system, including hydrocephalus and a dorsally restricted malformation of the spinal cord. These mice also display homeotic transformations of vertebrae in the midthoracic and lumbar regions. Homozygous s^27Pub mice contain a point mutation in the piebald gene, survive to weaning, and display no central nervous system or skeletal defects, arguing that the s^15DttMb phenotype results from the loss of genes in addition to piebald. A larger deletion, s^36Pub, exhibits additional cartilage malformations and defects in the anterior axial and cranial skeleton. The skeletal defects in both s^15DttMb and s^36Pub mice resemble transformations associated with the targeted disruption of Hox genes and genes encoding the retinoic acid receptors, which play a role in the specification of segmental identity along the anteroposterior axis. Complementation analysis of the s^15DuMb and s^36Pub phenotypes, using two additional deletions, localized the gene(s) associated with each phenotype to a defined chromosomal region.