This targeted mutation of zinc finger protein of the cerebellum 1 and 4 (Zic1/Zic4) gene displays ataxia, cerebellar hypoplasia and foliation defects; and may be useful in the study of cerebellar development and as a model for Dandy-Walker malformation.
Kathleen Millen, Seattle Children's Hospital Research Ins
Mice heterozygous for mutations in both genes exhibit two distinct phenotypes. Similar to mice heterozygous for Zic4tm2Kjmi, 85% of mice have grossly normal cerebellar anatomy, while the remaining 15% develop severe cerebellar size and foliation defects, disproportionate hypoplasia of the vermis, ataxia, reduced body weight, abnormal righting reflexes and do not survive past weaning. Cerebellar abnormalities in these mice resemble those seen in human Dandy Walker malformation, which is identifed by reduced cerebellar vermis size and is often accompanied by cerebellar ataxia and increased patient morbidity. Homozygous mice survive for approximately 2-3 weeks.
This mutant mouse strain may be useful in studies of cerebellar development and as a model for Dandy-Walker malformation.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A loxP flanked targeting vector containing neomycin resistance genes was used to replace the Zic4 exon 1 coding region, the 17.6 kb intergenic region and the entire first exon of of Zic1. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Transient Cre expression in targeted cells excised the neo cassette. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to 129S1/SvImJ and maintained as sibling matings. Upon arrival, mice were bred to 129S1/SvImJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Kathleen J Millen|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Zic4, zinc finger protein of the cerebellum 4|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A targeting vector was designed to replace the 17.6 kb region between Zic1 and Zic4, as well as the coding region of the first exon of Zic4 and the entire first exon of Zic1. Transient Cre expression removed the neo in ES cells.|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation survive for only 2-3 weeks.
When using the 129-Zic1/Zic4tm1Kjmi/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012561 in your Materials and Methods section.