A Defect in Nurturing in Mice Lacking the Immediate Early Gene fosB

AbstractAlthough expression of the Fos family of transcription factors is induced by environmental stimuli that trigger adaptive neuronal responses, eidence that Fos family members mediate these responses is lacking. To address this issue, mice were generated with an inactivating mutation in the fosB gene. fosB mutant mice are profoundly deficient in their ability to nurture young animals but are normal with respect to other cognitive and sensory functions. The nurturing defect is likely due to the absence of FosB in the preoptic area, a region of the hypothalamus that is critical for nurturing. These observations suggest that a transcription factor controls a complex behavior by regulating a specific neuronal circuit and indicate that nurturing in mammals has a genetic component

Partial rescue of the p35-/- brain phenotype by low expression of a neuronal-specific enolase p25 transgene

Cyclin-dependent kinase 5 (Cdk5) is activated on binding of activator proteins p35 and p39. A N-terminally truncated p35, termed p25, is generated through cleavage by the Ca 2 �-dependent protease calpain after induction of ischemia in rat brain. p25 has been shown to accumulate in brains of patients with Alzheimer’s disease and may contribute to A- � peptide-mediated toxicity. Studies from transfected neurons as well as p35 and p25 transgenic mice have indicated that Cdk5, when activated by p25, gains some toxic function compared with p35/Cdk5. It remains unclear, however, whether p25/Cdk5 signaling additionally channels into pathways usually used by p35/Cdk5 and whether p25 is associated with a loss of p35 function. To clarify these issues, we have generated p25-transgenic mice in a p35-null background. We find that low levels of p25 during development induce a partial rescue of the p35�/ � phenotype in several brain regions analyzed, including a rescue of cell positioning of a subset of neurons in the neocortex. In accordance with the partial rescue of brain anatomy, phosphorylation of the Cdk5 substrate mouse disabled 1 is partially restored during development. Besides this, p25/Cdk5 fails to phosphorylate other substrates that are normally phosphorylated by p35/Cdk5. Our results show that p25 can substitute for p35/Cdk

A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell

2Department of Neurology point to the general stage of neuronal development in which these proteins are necessary