A TRANSGENE INSERTION AT PERINATAL LETHALITY (PLE) IS ASSOCIATED WITHABNORMALITIES OF THE CORTEX

In an inbred genetic background, mice homozygous for a transgene inser tion at perinatal lethality (ple) were found to be significantly small er than their heterozygous or wild-type siblings at birth, and rarely survived for more than 48 h. Homozygous progeny of ple mice obtained f rom a cross with a different strain were viable, but were still not ob tained in the expected numbers, demonstrating some deleterious affect of this mutation even in a hybrid genetic background. Homozygous mice demonstrate variable expression of abnormalities in brain development. These usually appear as focal cortical ectopias, but also include oth er abnormalities, such as polymicrogyria. The genomic sequences corres ponding to the region disrupted by the transgene were cloned by isolat ing a junction fragment between transgenic and wild-type sequences, wh ich was then used to obtain the corresponding region of wild-type geno mic DNA. Since some probes from this region do not hybridize with geno mic DNA from homozygous ple mice, it appears likely that a deletion ev ent coincided with the transgene insertion.