Complementation mapping of skeletal and central nervous system abnormalities in mice of the piebald deletion complex
O'Brien, T.P.; Metallinos, D.L.; Chen, H.; Shin, M.K.; Tilghman, S.M.
Genetics 143(1): 447-461
1996
ISSN/ISBN: 0016-6731 PMID: 8722795 Document Number: 455594
The s-15DttMb, s-36Pub, s-1Acrg 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-15DttMb and s-36Pub phenotypes, using two additional deletions, localized the gene (s) associated with each phenotype to a defined chromosomal region.