Novel Alternative Splice Variants of Mouse Cdk5rap2

Autosomal recessive primary microcephaly(MCPH) is a rare neurodevelopmental disordercharacterized by a pronounced reduction of brain volume and intellectual disability. A current model for the microcephalyphenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlightof stem cell biologyand neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5regulatory subunit-associated protein 2 gene CDK5RAP2are one genetic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephalyphenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2gene that are at least in part accountable for the lack of microcephalyin the mice.