Pleiotropic effects in Eya3 knockout mice.
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.
Söker
Torben
T
Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Developmental Genetics, Neuherberg, Germany. tsoeker@web.de
Dalke
Claudia
C
Puk
Oliver
O
Floss
Thomas
T
Becker
Lore
L
Bolle
Ines
I
Favor
Jack
J
Hans
Wolfgang
W
Hölter
Sabine M
SM
Horsch
Marion
M
Kallnik
Magdalena
M
Kling
Eva
E
Moerth
Corinna
C
Schrewe
Anja
A
Stigloher
Christian
C
Topp
Stefanie
S
Gailus-Durner
Valerie
V
Naton
Beatrix
B
Beckers
Johannes
J
Fuchs
Helmut
H
Ivandic
Boris
B
Klopstock
Thomas
T
Schulz
Holger
H
Wolf
Eckhard
E
Wurst
Wolfgang
W
Bally-Cuif
Laure
L
de Angelis
Martin Hrabé
MH
Graw
Jochen
J
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
D004268:DNA-Binding Proteins; C466082:Eya3 protein, mouse; D029961:Zebrafish Proteins; D004247:DNA