Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1

Neurofibromatosis type 1 (NF1) is a commonly inherited autosomal dominant d isorder. Previous studies indicated that mice homozygous for a null mutatio n in Nf1 exhibit mid-gestation lethality, whereas heterozygous mice have an increased predisposition to tumors and learning impairments. Here we show that mice lacking the alternatively spliced exon 23a, which modifies the GT Pase-activating protein (CAP) domain of Nf1, are viable and physically norm al, and do not have an increased tumor predisposition, but show specific le arning impairments. Our findings have implications for the development of a treatment for the learning disabilities associated with NF1 and indicate t hat the CAP domain of NF1 modulates learning and memory.