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Table 3 MCPH animal models.

From: Molecular genetics of human primary microcephaly: an overview

MCPH gene Animal orthologs of human gene Animal model References
MCPH1 mcph1-/- (Drosophila/mice) Premature condensation of chromosome, non-coordinated centrosome, genome instability, detached centrosome, changes in cell cycle progression and defects in DNA damage repair, misregulated mitotic chromosome condensation. [25, 26, 29]
CDK5RAP2 Cnn-/- (Drosophila) Centrosome dysfunction causes connection loss between centrosomes and pericentriolar matrix. Only subtle defects of asymmetric divisions; the sizes of the observed brains were normal. [39]
ASPM asp-/- (Drosophila) Aspm-/-(mice) The Drosophila asp gene is vital for both the organisation and binding together of microtubules at the spindle poles and to focus the poles of the mitotic spindles during mitosis and meiosis. Two mutant mouse lines showed that mutations in ASPM decreased the brain size in mice. [5658]
CENPJ Sas-4-/-(Drosophila, c. elegans) Centrioles are lost due to damage of the CENPJ orthologue dsas-4 in Drosophila; in contrast, the knockout flies can live until adulthood but have weak coordination and lower viability. The morphological development of mutant flies is normal without cilia or flagella, but they die in early life. [65, 66]
STIL STIL Sil-/-(mice) STIL knockout mice (Sil-/-) exhibit numerous developmental abnormalities in embryonic days E7.5-8.5 and die after E10.5, the phenotype of the mutant mice is characterised by decreased brain size, restricted development, defective midline neural tube, abnormal development, and enhanced apoptosis; the observed mutants were embryonically lethal. [71]
CEP135 Bld10-/-(Chlamydomonas) In Chlamydomonas, CEP135 ortholog Bld10p mutants (bld10) demonstrated abnormal interphase microtubules and mitotic spindles, defects during cell division and a significant decrease in the growth rate. [73]
CEP152 Orthologous (Drosophila asterless; asl) CEP152 is the putative mammalian orthologue of Drosophila asterless, mutations in which affect mitosis in the fly. [77]
ZNF335 Orthologue (mice; ZNF335) Knockdown of ZNF335 caused a small brain size with an absent cortex and disrupted the proliferation and differentiation of neuronal cells. It was observed that knockdown of the ZNF335 ortholog in mice (ZFP335) resulted in early embryonic lethality at day E7.5. Conditional knockdown of ZNF335 in mouse cortical cells resulted in a small brain with a fundamentally absent cortex with deficient cortical neurons. [78]
  1. Abbreviations. MCPH1: Microcephalin; CDK5RAP2: Cyclin dependent kinase-5 regulatory subunit associated protein; ASPM: Abnormal spindle like primary microcephaly; CENPJ: Centromere-associated protein J; STIL: SCL/TAL1 interrupting locus; CEP135: Centrosomal protein 135; CEP152: Centrosomal protein 152; ZNF335: Zinc Finger Protein 335.