title: Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice.
abstract: Experiments involving overexpression of Ski have suggested that this gene is involved in neural tube development and muscle differentiation. In agreement with these findings, Ski-/- mice display a cranial neural tube defect that results in exencephaly and a marked reduction in skeletal muscle mass. Here we show that the penetrance and expressivity of the phenotype changes when the null mutation is backcrossed into the C57BL6/J background, with the principal change involving a switch from a neural tube defect to midline facial clefting. Other defects, including depressed nasal bridge, eye abnormalities, skeletal muscle defects and digit abnormalities, show increased penetrance in the C57BL6/J background. These phenotypes are interesting because they resemble some of the features observed in individuals diagnosed with 1p36 deletion syndrome, a disorder caused by monosomy of the short arm of human chromosome 1p (refs. 6-9). These similarities prompted us to re-examine the chromosomal location of human SKI and to determine whether SKI is included in the deletions of 1p36. We found that human SKI is located at distal 1p36.3 and is deleted in all of the individuals tested so far who have this syndrome. Thus, SKI may contribute to some of the phenotypes common in 1p36 deletion syndrome, and particularly to facial clefting.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. colmenc@ccf.org
authors.forename: Clemencia
authors.initials: C
authors.lastname: Colmenares
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Heilstedt
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Stuart
authors.initials: S
authors.lastname: Schwartz
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Ed
authors.initials: E
authors.lastname: Stavnezer
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005326:Fetal Proteins / Q000172:deficiency / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D009006:Monosomy; D009436:Neural Tube Defects / Q000235:genetics*; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D011519:Proto-Oncogenes; D013045:Species Specificity; D013577:Syndrome; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005326:Fetal Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C512653:Ski protein, mouse; D014157:Transcription Factors; C060614:SKI protein, human