title: Pleiotropic effects in Eya3 knockout mice.
abstract: BACKGROUND
  In Drosophila, mutations in the gene eyes absent (eya) lead to severe defects in eye development. The functions of its mammalian orthologs Eya1-4 are only partially understood and no mouse model exists for Eya3. Therefore, we characterized the phenotype of a new Eya3 knockout mouse mutant.
  
  
  RESULTS
  Expression analysis of Eya3 by in-situ hybridizations and beta-Gal-staining of Eya3 mutant mice revealed abundant expression of the gene throughout development, e.g. in brain, eyes, heart, somites and limbs suggesting pleiotropic effects of the mutated gene. A similar complex expression pattern was observed also in zebrafish embryos. The phenotype of young adult Eya3 mouse mutants was systematically analyzed within the German Mouse Clinic. There was no obvious defect in the eyes, ears and kidneys of Eya3 mutant mice. Homozygous mutants displayed decreased bone mineral content and shorter body length. In the lung, the tidal volume at rest was decreased, and electrocardiography showed increased JT- and PQ intervals as well as decreased QRS amplitude. Behavioral analysis of the mutants demonstrated a mild increase in exploratory behavior, but decreased locomotor activity and reduced muscle strength. Analysis of differential gene expression revealed 110 regulated genes in heart and brain. Using real-time PCR, we confirmed Nup155 being down regulated in both organs.
  
  
  CONCLUSIONS
  The loss of Eya3 in the mouse has no apparent effect on eye development. The wide-spread expression of Eya3 in mouse and zebrafish embryos is in contrast to the restricted expression pattern in Xenopus embryos. The loss of Eya3 in mice leads to a broad spectrum of minor physiological changes. Among them, the mutant mice move less than the wild-type mice and, together with the effects on respiratory, muscle and heart function, the mutation might lead to more severe effects when the mice become older. Therefore, future investigations of Eya3 function should focus on aging mice.
authors.affiliation: Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Developmental Genetics, Neuherberg, Germany. tsoeker@web.de
authors.forename: Torben
authors.initials: T
authors.lastname: Söker
authors.forename: Claudia
authors.initials: C
authors.lastname: Dalke
authors.forename: Oliver
authors.initials: O
authors.lastname: Puk
authors.forename: Thomas
authors.initials: T
authors.lastname: Floss
authors.forename: Lore
authors.initials: L
authors.lastname: Becker
authors.forename: Ines
authors.initials: I
authors.lastname: Bolle
authors.forename: Jack
authors.initials: J
authors.lastname: Favor
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hans
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kallnik
authors.forename: Eva
authors.initials: E
authors.lastname: Kling
authors.forename: Corinna
authors.initials: C
authors.lastname: Moerth
authors.forename: Anja
authors.initials: A
authors.lastname: Schrewe
authors.forename: Christian
authors.initials: C
authors.lastname: Stigloher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Topp
authors.forename: Valerie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Beatrix
authors.initials: B
authors.lastname: Naton
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Boris
authors.initials: B
authors.lastname: Ivandic
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Laure
authors.initials: L
authors.lastname: Bally-Cuif
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005123:Eye / Q000196:embryology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D017403:In Situ Hybridization; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D009154:Mutation; D009928:Organ Specificity; D010641:Phenotype; D011247:Pregnancy; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C466082:Eya3 protein, mouse; D029961:Zebrafish Proteins; D004247:DNA