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Overview

Disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development. There appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and the entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. Along with these brain defects, Nfix-/- animals also show a failure to thrive beginning at ~P8 that may be due to intestinal defects. Most Nfix-/- die by P22 on a normal diet but can survive if fed a soft dough, high fat diet. Severe malnutrition in the Nfix-/- animals may be related to skeletal defects seen in one strain of Nfix-/- mice.

Figures
FIGURE 1 Fig. 1. Failure to thrive in Nfix-/- animals and delays eye and ear canal opening
From Campbell et al. BMC Dev. BIol. 2008, 8:52. Delayed weight gain and development in Nfix-/- animals. A) Reduced weight gain in Nfix-/- animals on regular chow. The weights of progeny of Nfix-/+ parents were measured and plotted according to genotype. Note that Nfix-/- animals showed a slower weight gain from ~P6 and died at ~P22 when maintained on standard lab chow. Closed circles, WT (+/+); gray circles, Nfix-/+ (HET); open circles, Nfix-/- (KO). B) Increased weight gain of Nfix-/- animals fed a soft dough diet. The cages containing litters of Nfix-/+ parents were supplemented from P10 with soft transgenic dough. Weight gain and survival were increased substantially compared to non-supplemented litters (e.g. 2A). Symbols are as in panel A. C) Delay in eyelid opening in Nfix-/- mice. Eyelid opening was measured at various times after birth in progeny of Nfix-/+ animals. Nfix-/- animals showed an ~2 day delay in eyelid opening. Closed circles, WT (+/+); closed squares, HET (Nfix-/+); open circles, KO (Nfix-/-). The numbers following the genotype indicate the number of animals analyzed. D) Delay in ear canal opening in Nfix-/- mice. The opening of the ear canal was assessed at various times after birth in progeny of Nfix-/+ animals. Nfix-/- (KO) animals showed an ~4 day delay in ear canal opening. Symbols are as in panel C. The data in panels C and D are from an ~50% mixture of dough-supplemented and non-supplemented litters.
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