Genetics, Vol 141, 321-332, Copyright © 1995

INVESTIGATIONS

Phenotypic and Molecular Analysis of a Transgenic Insertional Allele of the Mouse Fused Locus

W. L. Perry-III, T. J. Vasicek, J. J. Lee, J. M. Rossi, L. Zeng, T. Zhang, S. M. Tilghman and F. Costantini
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032 Present address: Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702.

Spontaneous mutations at the mouse Fused (Fu) locus cause dominant skeletal and neurological defects and recessive lethal embryonic defects including neuroectodermal abnormalities and axial duplications. Here, we describe a new allele at the Fu locus caused by a transgenic insertional mutation, H{epsilon}46. Embryos homozygous for the H{epsilon}46 insertion die at day 9-10 post coitum and display phenotypic defects similar to those associated with Fu alleles. The H{epsilon}46 locus was cloned and shown to contain a 20-kb deletion at the site of transgene insertion with no other detectable rearrangements. Genomic probes from the H{epsilon}46 locus were mapped to a genetic locus closely linked to Fu on chromosome 17 and were hybridized to a YAC contig covering the Fu(Ki) critical region. Compound heterozygotes between H{epsilon}46 and Fu(Ki) were inviable and displayed abnormalities at the same stage of embryogenesis as do homozygotes for either of the two mutations, demonstrating that these two recessive lethal mutations belong to the same complementation group. A genomic probe from the wild-type H{epsilon}46 locus detected a transcript that is disrupted by the transgenic insertion, representing a candidate for the wild-type allele of Fused.

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