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Essential genes for embryogenesis uncovered in major mouse mutagenesis project

ITHACA, NY, Fri., July 15, 2005 A team of scientists led by Cornell University's Dr. John Schimenti reports today that an extraordinary number of genes are required for prenatal mammalian development. The researchers estimate that up to 19% of all genes are vital for embryogenesis in mice. Their study, which is one of the largest functional genomics projects described to date, is published in today's online edition of the journal Genome Research.

In addition to the important implications for understanding mammalian developmental biology and the genetic basis for spontaneous abortions, the impressive scale of the study an enormous logistical effort spanning the past six years marks a major step forward in the functional annotation of the mouse genome.

"Due to the availability of whole-genome sequences, we are now in the powerful position of knowing the sequence identity of most genes, their locations in the genome, their expression patterns, and which proteins interact with one another," explains Schimenti. "However, identifying the functions of these genes is a much more difficult challenge. For most genes, direct experimentation in the context of a whole organism will be required."

In an effort to explore the functional content of 50 megabases of mouse chromosome 5, or approximately 2% of the genome, Schimenti and his colleagues generated over 1000 mouse pedigrees with random mutations using a chemical called N-ethyl-N-nitrosourea (ENU). They then screened offspring from these pedigrees for lethality and defects in behavior, fertility, fitness, hearing, and vision.

Of 42 mutations identified, an overwhelming majority 34 mutations resulted in embryonic lethality. The scientists attributed the lethality to defects in processes including cellular proliferation, gastrulation, cardiovascular function, craniofacial development, neural tube development, and placental development.

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Contact: Maria A. Smit
smit@cshl.edu
516-422-4013
Cold Spring Harbor Laboratory
14-Jul-2005


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