Most homozygous Cic (capicua homolog (Drosophila)) hypomorphic mice die around postnatal day 21. Those that survive show a lung alveolarization defect and have reduced expression of Atxn1 (ataxin 1), a gene associated with spinocerebellar ataxia type I.
Huda Zoghbi, Baylor College of Medicine
Cic (capicua homolog (Drosophila)) is a transcriptional repressor gene regulated by Egf (epidermal growth factor).
Most homozygous Cic gene-trap mice die around postnatal day 21 (P21). Those that survive are smaller than their littermates and show a lung alveolarization defect. They lack expression of the Cic-L (long) isoform, but express reduced levels (~15%) of Cic-S (short) isoform in the lung and cerebellum. As such, this allele is considered to be a hypomorph.
Heterozygotes express both the Cic-L and Cic-S isoforms at about 50% normal levels. Disruption of the Cic gene is accompanied by a proportionate reduction in the expression of Atxn1 (ataxin 1) and Atxn1l (ataxin 1-like) in the cerebellum, confirming the interdependency of the genes. Mutations in Atxn1 are associated with spinocerebellar ataxia type I (SCA1).
Bay Genomics gene trap ES cell line XE565, generated in 129P2/Ola-derived E14Tg2a.4 embryonic stem cells, was used to produce these mice. The gene trap vector contained a splice-acceptor sequence upstream of beta-geo (a fusion of beta-galactosidase and neomycin phosphotransferase II), and was inserted into an intronic or coding region of genomic DNA just 3' of the Cic-L isoform. This created a fusion transcript containing sequences from exons upstream of the insertion joined to the beta-geo marker, disrupting the gene. No Cic-L isoform is produced and levels of Cic-S protein are 90% reduced. The donating laboratory backcrossed this line to C57BL/6 for 10 generations.
|Allele Name||gene trap XE565, BayGenomics|
|Allele Type||Gene trapped|
|Gene Symbol and Name||Cic, capicua transcriptional repressor|
|Gene Synonym(s)||1200010B10Rik; 1200010B10Rik; MRD45; RIKEN cDNA 1200010B10 gene; mKIAA0306|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||The gene trap vector inserted downstream of exon 1. The absence of protein expression of the long isoform was confirmed by western blot anaylsis. The expression of the short isoform is reduced to 10% of wild-type.|
|Mutations Made By|| |
Huda Zoghbi, Baylor College of Medicine
Heterozygotes are viable and fertile. Most homozygotes die around postnatal day 21 (P21)
When using the B6.129P2-CicGt(XE565)Byg/HzoJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #018133 in your Materials and Methods section.
|Heterozygous or wildtype for Cic<Gt(XE565)Byg>|
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