title: Generation of an 870 kb deletion encompassing the Skt/Etl4 locus by combination of inter- and intra-chromosomal recombination.
abstract: BACKGROUND
  Etl4(lacZ) (Enhancer trap locus 4) and Skt(Gt) (Sickle tail) are lacZ reporter gene integrations into the same locus on mouse chromosome 2 targeting a gene that is expressed in the notochord of early embryos and in multiple epithelia during later development. Both insertions caused recessive mutations that resulted exclusively in mild defects in the caudal vertebral column. Since notochord-derived signals are essential for formation of the vertebral column the phenotypes suggested that the lacZ insertions interfered with some notochord-dependent aspect of vertebral development. As both insertions occurred in introns it was unclear whether they represent hypomorphic alleles or abolish gene function. Here, we have generated a definitive null allele of the Skt/Etl4 gene and analysed homozygous mutants.
  
  
  RESULTS
  We have introduced loxP sites into three positions of the gene based on additional upstream exons that we identified, and deleted approximately 870 kb of the locus by a combination of inter- and intra-chromosomal Cre-mediated recombinations in the female germ line of mice. This deletion removes about 90 % of the coding region and results in the loss of the SKT/ETL4 protein. Similar to the Etl4(lacZ) and Skt(Gt) alleles our deletion mutants are viable and fertile and show only mild defects in caudal vertebrae due to abnormal intervertebral disc development, although with higher penetrance. No other tissue with Skt/Etl4 expression that we analysed showed obvious defects.
  
  
  CONCLUSIONS
  The complete loss of Skt/Etl4 function affects only development of caudal notochord derivatives and is compensated for in its other expression domains.
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. ausmeier.katrin@mh-hannover.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Serth
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. beckers.anja@mh-hannover.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Beckers
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. schuster-gossler.karin@mh-hannover.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Schuster-Gossler
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. mpavlova@uw.edu.|Department of Anaesthesiology and Pain Medicine, University of Washington, Seattle, WA, 98001, USA. mpavlova@uw.edu.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Pavlova
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. juliamueller2408@gmx.de.|, Gasteiner Str. 31, 10717, Berlin, Germany. juliamueller2408@gmx.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Müller
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. mariel.paul@meduniwien.ac.at.|Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria. mariel.paul@meduniwien.ac.at.
authors.forename: Mariel C
authors.initials: MC
authors.lastname: Paul
authors.affiliation: Max Planck-Genome-Centre Cologne, Carl-von-Linné-Weg 10, D-50829, Köln, Germany. reinhardt@mpipz.mpg.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Reinhardt
authors.affiliation: Institut für Molekularbiologie OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany. gossler.achim@mh-hannover.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Gossler
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D017353:Gene Deletion; D018390:Gene Targeting / Q000379:methods*; D017930:Genes, Reporter; D007403:Intervertebral Disc / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D013623:Tail / Q000196:embryology
chemical_list: D011506:Proteins; C579020:Skt protein, mouse