Mice carrying this ENU-generated mutant Crppa (CDP-L-ribitol pyrophosphorylase A) allele express a truncated protein. Homozygous mutants have defective glycosylation of dystroglycan, resulting in a number of neurodevelopmental phenotypes.
David D. Ginty, Harvard Medical School
Crppa (CDP-L-ribitol pyrophosphorylase A) is required for the glycosylation of dystroglycan and the regulation of axonal guidance during embryonic development.
This strain carries an ENU-generated T to A mutation in exon 1 of the gene that converts leucine 79 to a premature stop codon (L79*), creating a truncation in the expressed protein. Homozygous mutants have defective glycosylation of dystroglycan, resulting in a number of neurodevelopmental phenotypes. This includes disruptions in the formation of the axon tracts that form dorsal funiculus and the vetrolateral funiculus in the spinal cord. Mutants also exhibit a breakdown of the basal lamina in the cortex, resulting in cortical migration defects and the development of cobblestone lissencephaly.
Homozygous embryos can be obtained at normal Mendelian ratios up to embryonic day 18.5 (E18.5), but mutants that are born die immediately after birth due to apparent respiratory failure. Heterozygotes are viable and fertile.
ENU-mutagenized C57BL/6 males were crossed with C3H/He females as part of a three-generation, forward genetic screen for embryos with axonal guidance and branching defects. Line 9445 mice carry a T to A mutation in Crppa which converts leucine 79 to a stop codon (L79), resulting in an early truncation of the protein. This strain was backcrossed to C3H/HeJ for approximately 6 generations by the donating lab.
|Allele Name||mutation 1, David D Ginty|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||ISPDL79*; Line 9445|
|Gene Symbol and Name||Crppa, CDP-L-ribitol pyrophosphorylase A|
|Strain of Origin||C57BL/6|
|Molecular Note||ENU induced a T to A mutation in Line 9445 that converts leucine 79 to a stop codon (L79) and results in an early truncation of the protein.|
Heterozygotes are viable and fertile. Homozygotes are neonatal lethal.
When using the C3.B6-Crppam1Ddg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022019 in your Materials and Methods section.