129S1.129P-Nr2e1^frc/EmsMmjax

Stock number: 038755
Product name: fierce
Research areas: Developmental Biology Research, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research

Description

Nr2e1^frc (fierce) is spontaneous recessive mutation that results in a null allele of the Nr2e1 (nuclear receptor subfamily 2, group E, member 1, also known as TLX) gene. Homozygous mice are characterized by extreme aggression, blindness, and cerebral hypoplasia. This strain may be useful for studying retinal, brain and behavioral abnormalities.

Of note, fierce mice on the C57BL/6J congenic background are distributed as B6.129P2-Nr2e1^frc/EmsMmjax (MMRRC Stock No. 071402).

Detailed description

Nr2e1 (nuclear receptor subfamily 2, group E, member 1, also known as TLX) is an intracellular transcription factor involved in regulation of adult neural stem cell proliferation, brain-eye coordination, and control of aggressive behavior.

The recessive, spontaneous Nr2e1^frc mutation has been identified as a 44.4 kb deletion that includes the Nr2e1 coding and untranslated regions. Mice homozygous for the mutation are viable and fertile but unsuited for breeding due to aggressive behavior and poor mothering. Homozygous mutants exhibit stunted growth, hypoplasia of the cerebellum and olfactory lobes, reduced neural stem/progenitor cell proliferation, extreme aggression, extreme hyperactivity, retinal abnormalities (resulting in blindness), and deficits in fear conditioning. On the C57BL/6J background, mice are highly aggressive, and develop hydrocephalus (30% incidence) and enlarged ventricles. On the 129 background (this strain), mice have little or no hydrocephalus, exhibit a deficiency in the size and number of retinal vessels, and are less aggressive, but have very small litters; lack of maternal behavior is less evident in the 129 background.

Of note, fierce mice on the C57BL/6J congenic background are distributed as B6.129P2-Nr2e1^frc/EmsMmjax (MMRRC Stock No. 071402).

Development

The spontaneous fierce mutation, Nr2e1^frc, occurred during the gene targeting of Zfa gene using 129P2/OlaHsd-derived E14TG2a embryonic stem cells. The mutation is believed to have arisen during electroporation and was not present in the ES cells (Kumar RA et al. 2004, PMID: 14994267). Mice homozygous for the mutation were identified by abnormal brains and violent behavior. Chimeric mice were bred to both C57BL/6J and 129P3/JEms mice. Mice were than bred to 129S1/SvImJ for 6 generations. Segregation of the aggressive phenotype from the Zfa null mice occurred during backcrossing. Embryos were cryopreserved in 1998 at generation N6F1N2+N1. The fierce mutation was identified as a 44.4 kb deletion in Nr2e1 on chromosome 10 that includes all coding and untranslated regions but no exons from the adjacent genes, Lace1 and Snx3. In addition, there is a 188 bp insertion that interrupts the deletion breakpoints.

Allele

Symbol: Nr2e1^frc
Name: fierce
MGI accession ID: MGI:2176490
Generation method: Spontaneous
Marker symbol: Nr2e1
Marker name: nuclear receptor subfamily 2, group E, member 1
Marker synonyms: Mtll; tailless; TLL; Tlx; XTLL
Chromosome: 10
Strain of origin: 129P2/OlaHsd
Molecular note: The underlying mutation responsible for the phenotype in the fierce mouse was identified as a deletion in the Nr2e1 gene. The genomic deletion was confirmed by Southern analysis and no transcript was detectable by Northern analysis in homozygous mutant animals. Presence of a human BAC transgene containing the NR2E1 gene rescues the phenotype of mice homozygous for the fierce mutation. J:99431