Mouse knockout of Nuclear factor I genes cause cortical malformations that persist into adulthood

Bunt J1, Boogert S1, Lim JWC1, Huth SF1, Dean RJ1, Bridges C1, Gronostajski RM2 and Richards LJ1

  1. The University of Queensland, Queensland Brain Institute, Brisbane, Australia.
  2. State University of New York at Buffalo, Department of Biochemistry- Program in Genetics- Genomics and Bioinformatics- Center of Excellence in Bioinformatics and Life Sciences, Buffalo, USA.

The Nuclear factor I (NFI) family of transcription factors are required for the development of multiple organ systems. Using mouse knockout models, we previously demonstrated that family members NFIA, NFIB and NFIX are important for normal brain development. These proteins have overlapping biological functions in regulating the transition of progenitor cells from proliferation to differentiation and therefore result in overlapping neurodevelopmental defects in embryos. Nfia and Nfib knockout mice die at birth due to kidney and lung defects, respectively. To investigate whether the phenotypes observed in embryonic development persist into adulthood, we generated cortex-specific conditional knockout mouse models of Nfia and Nfib. These Nfiaflox or Nfibflox; Emx1-Cre mice are viable and fertile. Their postnatal cortical development is delayed, but no major defects are observed. In adulthood, these mutants have enlarged brains due to increased volume of the cerebral cortex and, in particular, the cingulate cortex. Preliminary assessment revealed only a minor behavioural phenotype. These observed phenotypes are comparable to those in humans with a deletion or mutation of NFI. Hence, we now have a model to further study the aetiology and the functional defects in the human disorders.