Interaction between undulated and Patch leads to an extreme form of spina bifida in double-mutant mice

• Published in: Nature genetics Vol. 11; no. 1; pp. 60 - 63
• Main Authors: Helwig, Ute, Imai, Kenji, Schmahl, Wolfgang, Thomas, Bianca E, Varnum, Don S, Nadeau, Joseph H, Balling, Rudi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.09.1995
• Subjects: Abnormalities, Multiple - embryology; Abnormalities, Multiple - genetics; Animals; Biological and medical sciences; Classical genetics, quantitative genetics, hybrids; Crosses, Genetic; Cysts - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genes, Lethal; Genetics of eukaryotes. Biological and molecular evolution; Humans; Mesoderm - pathology; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Morphogenesis - genetics; Paired Box Transcription Factors; Pigmentation Disorders - genetics; Platelet-Derived Growth Factor - deficiency; Platelet-Derived Growth Factor - genetics; Platelet-Derived Growth Factor - physiology; Point Mutation; Sequence Deletion; Spinal Dysraphism - embryology; Spinal Dysraphism - genetics; Spine - embryology; Transcription Factors - genetics; Transcription Factors - physiology; Vertebrata; Animal model; Genetic inheritance; Gene interaction; Pathogenesis; Rodentia; Diseases of the osteoarticular system; Spine disease; Congenital disease; Spina bifida; Vertebrata; Mammalia; Gene; Mouse; Malformation; Mutation
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0995-60

The aetiology of spina bifida involves genetic and environmental factors, which may be why major genes contributing to pathogenesis have not been identified. Here we report that undulated-Patch double-mutant mice have a phenotype reminiscent of an extreme form of spina bifida occulta in humans. This unexpected phenotype in double-mutant but not single-mutant mice shows that novel congenital anomalies such as spina bifida can result from interaction between products of independently segregating loci. This example of digenic inheritance may explain the often sporadic nature of spina bifida in humans.