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Nr2e1frc (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 129S1 congenic background are distributed as 129S1.129P-Nr2e1frc/EmsMmjax (MMRRC Stock No. 071401).
The spontaneous fierce mutation, Nr2e1frc, 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. Segregation of the aggressive phenotype from the Zfa null mice occurred during backcrossing. Embryos were cryopreserved in 1998 at generation N10F1N3. 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.
Abrahams BS, Kwok MC, Trinh E, Budaghzadeh S, Hossain SM, Simpson EM. Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1. J Neurosci. 2005 Jul 6;25(27):6263-70. doi: 10.1523/JNEUROSCI.4757-04.2005. Erratum in: J Neurosci. 2005 Aug 3;25(31):table of contents. (Medline PMID: 16000615)
Abrahams BS, Mak GM, Berry ML, Palmquist DL, Saionz JR, Tay A, Tan YH, Brenner S, Simpson EM, Venkatesh B. Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci. Genomics. 2002 Jul;80(1):45-53. doi: 10.1006/geno.2002.6795. (Medline PMID: 12079282)
Kumar RA, Chan KL, Wong AH, Little KQ, Rajcan-Separovic E, Abrahams BS, Simpson EM. Unexpected embryonic stem (ES) cell mutations represent a concern in gene targeting: lessons from "fierce" mice. Genesis. 2004 Feb;38(2):51-7. doi: 10.1002/gene.20001. (Medline PMID: 14994267)
Young KA, Berry ML, Mahaffey CL, Saionz JR, Hawes NL, Chang B, Zheng QY, Smith RS, Bronson RT, Nelson RJ, Simpson EM. Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Behav Brain Res. 2002 May 14;132(2):145-58. doi: 10.1016/s0166-4328(01)00413-2. (Medline PMID: 11997145)
Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.
The donor or their institution limits the distribution to non-profit institutions only.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.