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Sensitivity of mouse brain development to Zfp423 mutations.

Dorsal surface and block face micrographs of unaffected (left), Zfp423-hypomorphic (middle), and Zfp423-null (right) mutant brains show sensitivity of midline structures to reduced Zfp423 function. Brain development requires coordination among cell lineage and extracellular signaling information. Zfp423's zinc finger domains bind DNA and other regulatory proteins in lineage- and signal-dependent contexts, including EBF, SMAD, retinoic acid receptor, notch intracellular domain, and DNA damage response proteins. Simple structural measures are sensitive to even heterozygous loss of Zfp423, allowing rapid phenotyping of variants. Among reported patient amino acid substitution variants, however, only H1277Y, which disrupts an EBF-binding zinc finger, shows an effect. See Deshpande et al.

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Image Credit: Ojas Deshpande