Inactivation of the gene for the nuclear receptor tailless in the brain preserving its function in the eye.
During embryogenesis, tailless, an orphan member of the nuclear receptor family, is expressed in the germinal zones of the brain and the developing retina, and is involved in regulating the cell cycle of progenitor cells. Consequently, a deletion of the tailless gene leads to decreased cell number with associated anatomical defects in the limbic system, the cortex and the eye. These structural abnormalities are associated with blindness, increased aggressiveness, poor performance in learning paradigms and reduced anxiousness. In order to assess the contribution of blindness to the behavioural changes, we established tailless mutant mice with intact visual abilities. We generated a mouse line in which the second exon of the tailless gene is flanked by loxP sites and crossed these animals with a transgenic line expressing the Cre recombinase in the neurogenic area of the developing brain, but not in the eye. The resulting animals have anatomically indistinguishable brains compared with tailless germline mutants, but are not blind. They are less anxious and much more aggressive than controls, like tailless germline mutants. In contrast to germline mutants, the conditional mutants are not impaired in fear conditioning. Furthermore, they show good performance in the Morris water-maze despite severely reduced hippocampal structures. Thus, the pathological aggressiveness and reduced anxiety found in tailless germline mutants are due to malformations caused by inactivation of the tailless gene in the brain, but the poor performance of tailless null mice in learning and memory paradigms is dependent on the associated blindness.
Belz
Thorsten
T
Division of Molecular Biology of the Cell I, German Cancer Research Center, D-69120 Heidelberg, Germany.
Liu
Hai-Kun
HK
Bock
Dagmar
D
Takacs
Andrea
A
Vogt
Miriam
M
Wintermantel
Tim
T
Brandwein
Christiane
C
Gass
Peter
P
Greiner
Erich
E
Schütz
Günther
G
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D004622:Embryo, Mammalian; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D005239:Fear / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011506:Proteins / Q000378:metabolism; D022661:RNA, Untranslated; D011930:Reaction Time / Q000235:genetics / Q000528:radiation effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000502:physiology; D012737:Sex Factors
C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C490258:Nr2e1 protein, mouse; D011506:Proteins; D022661:RNA, Untranslated; D018160:Receptors, Cytoplasmic and Nuclear; D017871:Calcium-Calmodulin-Dependent Protein Kinases