This strain carries a null allele of the transcription factor Nr4a2 (also called Nurr1), which is associated with the development of midbrain dopaminergic neurons. Mice exhibit alterations in dopamine levels and abnormal behavioral and locomotor responses associated with schizophrenia.
Thomas Perlmann, Karolinska Institut
The transcription factor Nr4a2 (also called Nurr1) is associated with the development of midbrain dopaminergic neurons. These neurons play a role in movement, emotion, motivation and working memory. Alterations in dopamine neurotransmission are implicated in schizophrenia. Mice homozygous for the null allele fail to develop dopaminergic neurons, become hypoactive and die within 2 days of birth. Heterozygous mice are viable, fertile, normal in size and do not display any gross physical abnormalities. Although there are significant gender differences, both males and females exhibit hyperactivity and an impairment of passive avoidance retention. In the forced swim test, male mice exhibit a depression-like profile of immobility and low activity. Dopamine turnover in males is reduced in the striatum and enhanced in the prefrontal cortex, while in females the reverse is observed. This mutant mouse strain may be useful in studies of schizophrenia.
A targeting vector was designed to replace coding exons 2, 3, and part of coding exon 4 with a neomycin cassette; the region encompasses the N-terminal transactivation and DNA binding domains of the nuclear receptor subfamily 4, group A, member 2 (Nr4a2) gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reported that the resulting chimeric animals were crossed to C57BL/6N mice for a minimum of nine of generations (see SNP note below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 27 markers throughout the genome segregates with 129. All 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6N. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Thomas Perlmann|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Nr4a2, nuclear receptor subfamily 4, group A, member 2|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Insertion of a neomycin resistance cassette replaces the sequence encoding the N terminal transactivation and DNA binding domains (exons 2,3 and part of 4). In situ hybridization detected no transcript from this gene in homozygous mutant mice.|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation die within two days of birth.
When using the Nurr1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017859 in your Materials and Methods section.