Zfp335 (zinc finger protein 335; also known as identified as a NRC-interacting factor 1 (Nif1)) is a regulator of vertebrate neurogenesis. A c.3332g>a mutation in the human gene is associated with severe microcephaly, neuronal degeneration, and neonatal death. The mouse Zfp335 promoter, exon 1, and exon 2 are flanked by loxP sites in this conditional targeted mutation strain, enabling tissue-specific knockouts mediated by Cre recombinase.
Christopher Walsh, Boston Children's Hospital
Zfp335 (zinc finger protein 335; also known as NRC-interacting factor 1 (Nif1)) is a regulator of vertebrate neurogenesis. As a component of the trithorax H3K4-methylation complex that regulates REST/NRSF, it is essential for neural cell progenitor self-renewal, neurogenesis, and neuronal differentiation. A c.3332g>a mutation in the human gene is associated with severe microcephaly, neuronal degeneration, and neonatal death.
In this targeted mutation strain, the mouse Zfp335 promoter, exon 1, and exon 2 are flanked by loxP sites. Cre-mediated excision of this floxed region enables the generation of tissue-specific knockouts. Widespread loss of ZNF335 protein in mice leads to embryonic lethality as early as embryonic day 7.5 (E7.5).
When crossed with Emx1-cre mice (see Stock No. 005628), progeny lack almost all cortical structure and cortical neurons, leading to the formation of a small brain with a thin sheath of tissue and enlarged ventricles.
The promoter, exons 1 and 2 and a FRT-flanked neomycin cassette in intron 2 were flanked by loxP sites in (d/SvEvTac x C57BL/6J)F1-derived PTL1 embryonic stem (ES) cells. Resultant male chimeric mice were crossed with ACTB-Flp mice backcrossed to C57BL/6 to excise the neomycin cassette. This strain was backcrossed to C57BL/6 for 7 generations by the donating laboratory (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. Four of the 27 markers throughout the genome were segregating, suggesting an incomplete backcross. Also, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1.1, Christopher A Walsh|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Zfp335, zinc finger protein 335|
|Strain of Origin||(129S6/SvEvTac x C57BL/6J)F1|
|Molecular Note||Exons 1 and 2 were floxed. Flp-mediated recombination removed the FRT-flanked neo cassette inserted downstream of exon 2.|
Heterozygotes and homozygotes are viable and fertile.
When using the STOCK Zfp335tm1.1Caw/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022761 in your Materials and Methods section.