Forward genetics in the mouse continues to be a useful and unbiased approach to identifying new genes and alleles with previously unappreciated roles in mammalian development and disease. Here, we report a new mouse allele of
Cse1l that was recovered from an ENU
[...] Read more.
Forward genetics in the mouse continues to be a useful and unbiased approach to identifying new genes and alleles with previously unappreciated roles in mammalian development and disease. Here, we report a new mouse allele of
Cse1l that was recovered from an ENU mutagenesis screen. Embryos homozygous for the
anteater allele of
Cse1l display a number of variable phenotypes, with craniofacial and ocular malformations being the most obvious. We provide evidence that
Cse1l is the causal gene through complementation with a novel null allele of
Cse1l generated by CRISPR-Cas9 editing. While the variability in the
anteater phenotype was high enough to preclude a detailed molecular analysis, we demonstrate a very penetrant reduction in
Pax6 levels in the developing eye along with significant ocular developmental phenotypes. The eye gene discovery tool iSyTE shows
Cse1l to be significantly expressed in the lens from early eye development stages in embryos through adulthood.
Cse1l has not previously been shown to be required for organogenesis as homozygosity for a null allele results in very early lethality. Future detailed studies of
Cse1l function in craniofacial and neural development will be best served with a conditional allele to circumvent the variable phenotypes we report here. We suggest that human next-generation (whole genome or exome) sequencing studies yielding variants of unknown significance in
CSE1L could consider these findings as part of variant analysis.
Full article
