Novel Alternative Splice Variants of Mouse Cdk5rap2

Nadine Kraemer, Lina Issa-Jahns, Gerda Neubert, Ethiraj Ravindran, Shyamala Mani, Olaf Ninnemann, Angela M. Kaindl, Emanuele Buratti
2015 PLoS ONE  
Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by a pronounced reduction of brain volume and intellectual disability. A current model for the microcephaly phenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlight of stem cell biology and neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 are one
more » ... tic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2 LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephaly phenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2 gene that are at least in part accountable for the lack of microcephaly in the mice. Conditional Cdk5rap2 LoxP +/+ hCMV Cre + mice (cKO) were generated to obtain complete excision of the Cdk5rap2 exon 3 and introduce a stop codon in exon 4. Breeding of Cdk5rap2 LoxP +/+ mice with hCMV Cre + mice resulted in heterozygous Cdk5rap2 LoxP +/-hCMV Cre + mice which were then crossed with Cdk5rap2 LoxP +/+ mice. The latter mice were further breed Cdk5rap2 Splice Variant PLOS ONE |
doi:10.1371/journal.pone.0136684 pmid:26322982 pmcid:PMC4556188 fatcat:niks6wen5vgplp3k6cavny276y