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Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent.

A new spontaneous mouse mutation named fierce (frc) is deleted for the nuclear receptor Nr2e1 gene (also known as Tlx, mouse homolog of Drosophila tailless). The fierce mutation is genetically and phenotypically similar to Nr2e1 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-frc 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.

Pubmed ID: 11997145

Authors

  • Young KA
  • Berry ML
  • Mahaffey CL
  • Saionz JR
  • Hawes NL
  • Chang B
  • Zheng QY
  • Smith RS
  • Bronson RT
  • Nelson RJ
  • Simpson EM

Journal

Behavioural brain research

Publication Data

May 14, 2002

Associated Grants

  • Agency: NIDCD NIH HHS, Id: DC62108
  • Agency: NEI NIH HHS, Id: EY07758
  • Agency: NIMH NIH HHS, Id: MH/HD57465
  • Agency: NIMH NIH HHS, Id: MH57760
  • Agency: NIDCD NIH HHS, Id: R01 DC004301
  • Agency: NIDCD NIH HHS, Id: R01 DC004301-01
  • Agency: NIDCD NIH HHS, Id: R01 DC005827
  • Agency: NIDCD NIH HHS, Id: R01 DC005827-01
  • Agency: NEI NIH HHS, Id: R01 EY007758
  • Agency: NEI NIH HHS, Id: R01 EY007758-15
  • Agency: NIMH NIH HHS, Id: R01 MH057535
  • Agency: NIMH NIH HHS, Id: R01 MH057760
  • Agency: NIMH NIH HHS, Id: R01 MH057760-02
  • Agency: NIDCD NIH HHS, Id: R03 DC004376
  • Agency: NIDCD NIH HHS, Id: R03 DC004376-01A1
  • Agency: NIDCD NIH HHS, Id: R21 DC005846
  • Agency: NIDCD NIH HHS, Id: R21 DC005846-01A1
  • Agency: NIMH NIH HHS, Id: R21 MH083515-01

Mesh Terms

  • Aggression
  • Animals
  • Behavior, Animal
  • Blotting, Northern
  • Blotting, Southern
  • Brain
  • Corticosterone
  • Electroretinography
  • Eye Abnormalities
  • Female
  • Gene Deletion
  • Hearing
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear
  • Retina
  • Sexual Behavior, Animal
  • Smell
  • Testosterone