Abstract: Transgenic non-human animal models are described that allow for the fate mapping and identification of cells that respond to hedgehog signaling in vivo during a particular time period. More particularly, these animal models and cells obtained from these animal models may be used to screen for agonists or antagonists of the Hedgehog signaling pathway. Thus, these transgenic animal models allow for the identification of HH agonists or agents that may enhance neurogenesis or for HH antagonists or agents that may be potentially useful for treating cancers or hyperproliferative conditions associated with high levels of hedgehog expression.

Abstract: The present invention provides mice and mouse cell lines having a homozygous or heterozygous deficiency in a gene encoding a neurotrophin receptor. In a preferred embodiment of this invention, mice and cell lines carry a trkB locus specifically targeted within its tyrosine protein kinase sequences. Mice homozygous for this mutation express gp95.sup.trkB receptor of unknown function but not the high affinity functional gp145.sup.trkB tyrosine protein kinase receptors. This mutation results in multiple CNS and PNS neuronal deficiencies and in a postembryonic lethal phenotype. Such genetically modified mice are useful in model systems for studying human diseases involving neuronal degeneration and neuronal cell loss, as well as in screening for genes, proteins, or other compounds that may prevent or impede neuronal cell death or stimulate neuronal regeneration.