We describe a strategy for generating an allelic series of mutations at a given locus that requires the production of only one targetted mouse line. The 'allelogenic' mouse line we produced carries a hypomorphic allele of Fgf8, which can be converted to a null allele by mating to cre transgenic animals. The hypomorphic allele can also be reverted to wild-type by mating the allelogenic mice to flp transgenic animals, thereby generating a mouse line suitable for Cre-induced tissue-specific knockout experiments. Analysis of embryos carrying different combinations of these alleles revealed requirements for Fgf8 gene function during gastrulation, as well as cardiac, craniofacial, forebrain, midbrain and cerebellar development.
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