These mutant mice contain an ENU-induced premature stop codon in exon 9 of the Sec24b gene and may be useful in studying planar cell polarity, neural tube closure and convergent expansion in the developing embryo.
David D. Ginty, Harvard Medical School
Mice heterozygous for this ENU-induced mutation (Sec24bY613X), are viable and fertile, although the donating investigator reports that 33% of homozygous mice are dead or dying by E18.5. Sec24b is a cargo-sorting member of the core complex of the COPII endoplasmic reticulum (ER)-Golgi transport vesicle, and is critical for neural tube closure. These mice contain a premature stop codon in exon 9 of the Sec24 related gene family, member B (Sec24b) gene. Sec24bY613X homozygotes develop craniorachischisis, a fully open neural tube from the midbrain-hindbrain boundary to the most caudal end of the neural tube. These mice exhibit deficits in convergent extension and other planar cell polarity phenotypes. At E18.5, 45% of embryos exhibit omphalocele and 99% exhibit eyelid fusion failure. Also, outer and inner cochlear hair cells periodically fall out of phase and are abnormally aligned. These mutant mice may be useful in studying planar cell polarity, neural tube closure and convergent expansion in the developing embryo.
Male C57BL/6 mice were treated with multidose N-ethyl-N-nitrosourea (ENU) and then bred to C3H/He females. The resulting male pups were then bred to C3H/He females to obtain second generation mice. The resulting female offspring were subsequently bred back to their parental line to obtain third generation mice. A mutagenesis screen was then performed to select mice with mutations effecting neural development. A family of mice, line 811, exhibiting craniorachischisis was identified. A forward-genetic screen approach found mutations in the Sec24 related gene family, member B (Sec24b) gene. Sequencing of this gene identified two transcripts each with a T to A transversion in exon 9 resulting in a premature stop codon (Y613X and Y579X). Craniorachischisis was confirmed in mice harboring the Y613X mutation. These mice were backcrossed to C3H/He mice (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C3H/HeJ (Stock No. 000659) for at least one generation to establish the colony.
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. The 27 markers throughout the genome were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Sec24b811; Sec24bY613|
|Gene Symbol and Name||Sec24b, Sec24 related gene family, member B (S. cerevisiae)|
|Strain of Origin||C57BL/6|
|Molecular Note||ENU mutagenesis induced a T to A transversion in exon 9 (1834T>A in ENSMUST00000098616). This mutation results in an amino acid substitution of a stop codon at position 613 in a Sec23/24-binding domain instead of tyrosine (Y613X).|
|Mutations Made By|| |
David Ginty, Harvard Medical School
When maintaining a colony, heterozygous mice may be bred to wildtype mice from the colony or C3H/HeJ inbred mice (Stock No. 000659). The donating investigator reports that 33% of homozygous mice are dead or dying by embryonic day 18.5 (E18.5).
When using the STOCK Sec24bY613X/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #014645 in your Materials and Methods section.