Skeletal dysplasias, growth retardation, reduced postnatal survival, and impaired fertility in mice lacking the SNF2/SWI2 family member ETL1.
The mouse Etl1 gene encodes a nuclear protein belonging to the rapidly growing SNF2/SWI2 family. Members of this family are related to helicases and nucleic-acid-dependent ATPases and have functions in essential cellular processes such as transcriptional regulation, maintenance of chromosome stability and various aspects of DNA repair. The ETL1 protein is expressed from the two-cell stage onwards, throughout embryogenesis in a dynamic pattern with particularly high levels in the thymus, epithelia and the nervous system and in most adult tissues. As a first step to address the role of ETL1 in cells and during development, we inactivated the gene by homologous recombination. ES cells and mice lacking detectable ETL1 protein were viable, indicating that ETL1 is not essential for cell survival or for embryonic development. However, mutant mice showed retarded growth, peri/post natal lethality, reduced fertility and various defects in the sternum and vertebral column. Expressivity and penetrance of all observed phenotypes were influenced by the genetic background. Isogenic 129Sv(Pas) mice lacking ETL1 had a severely reduced thoracic volume, which might lead to respiratory failure and could account for the high incidence of perinatal death on this genetic background.
Schoor
M
M
Stanford University, School of Medicine, Department of Developmental Biology, Stanford, CA 94305-5427, USA. schoor@cmgm.stanford.edu
Schuster-Gossler
K
K
Roopenian
D
D
Gossler
A
A
D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005298:Fertility / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006130:Growth Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases