Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 132, Issue 2, Pages 145-158Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0166-4328(01)00413-2
Keywords
aggressive behaviour; sensorimotor; eye; brain
Categories
Funding
- NEI NIH HHS [EY07758, R01 EY007758-15, R01 EY007758] Funding Source: Medline
- NIDCD NIH HHS [R21 DC005846, R03 DC004376-01A1, R01 DC004301, R21 DC005846-01A1, R01 DC005827-01, R01 DC005827, R01 DC004301-01, DC62108] Funding Source: Medline
- NIMH NIH HHS [R01 MH057535, R01 MH057760-02, R01 MH057760, MH/HD57465, MH57760, R21 MH083515-01] Funding Source: Medline
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A new spontaneous mouse mutation named fierce (frc) is deleted for the nuclear receptor Nr2el gene (also known as Tlx, mouse homolog of Drosophila tailless). The fierce mutation is genetically and phenotypically similar Nr2el targeted mutations previously studied on segregating genetic backgrounds. However, we have characterized the fierce brain, eye, and behavioural phenotypes on three defined genetic backgrounds (C57BL/6J, 129P3/JEms, and B6129F1). The data revealed many novel and background-dependent phenotypic characteristics. Whereas abnormalities in brain development, hypoplasia of cerebrum and olfactory lobes, were consistent on all three backgrounds, our novel finding of enlarged ventricles in 100% and overt hydrocephalus in up to 30% of fierce mice were unique to the C57BL/6J background. Developmental eye abnormalities were also background-dependent with B6129F1-frc mice having less severe thinning of optic layers and less affected electroretinogram responses. Impaired regression of hyaloid vessels was observed in all backgrounds. Furthermore, retinal vessels were deficient in size and number in 129P3/JEms-frc and B6129F1-frc mice but almost entirely absent in C57BL/6J-frc mice. We present the first standardized behavioural tests conducted on Nr2e1 mutant mice and show that C57BL/6J-frc and B6129F1-frc mice have deficits in sensorimotor assays and are hyperaggressive in both sexes and backgrounds. However, C57BL/6J-jrc mice were significantly more aggressive than B6129F1-frc mice. Overall, this extensive characterization of the fierce mutation is essential to its application for the study of behavioural, and brain and eye developmental disorders. In addition, the background-dependent differences revealed will enable the identification of important genetic modifiers. (C) 2002 Elsevier Science B.V. All rights reserved.
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