By David N. Leff
MIAMI — In a mammalian embryo, "PAX" does not mean "peace," but a nine-member family of genes — PAX-1 through PAX-9 — that orchestrate early prenatal development.
At the Max Planck Institute of Biophysical Chemistry, in Göttingen, Germany, one focus of research is the family of PAX genes.
Molecular biologist Peter Grüss, the institute's director, was scheduled to speak at the 30th Miami Winter Biotechnology Symposia's functional genomics session on "Mouse mutants as models for mammalian development and human diseases."
However, having fractured his femur in a ski accident last month, Grüss deputized molecular biologist Luc St.-Onge, a senior scientist in his lab, to deliver his lecture.
"We have the PAX genes expressed throughout development, St.-Onge told his audience, but we don't know their function. To study function, you create mouse mutants and see what happens. PAX stands for 'paired box' in a DNA binding domain. The genes are transcription factors during embryogenesis.
"What we have in press in Nature Genetics," he continued, "is the functional analysis of the PAX-8 gene during thyroid development. It's expressed early in embryogenesis, involved in differentiation of thyroid-hormone-producing cells.
"When PAX-8 is absent — in our knockout mice, deleted," he continued, "then these cells are not being expressed, so they're not producing any thyroid hormones, and the mouse dies.
"In newborn human infants," St.-Onge pointed out, "where these hormones are not being produced, their absence leads to mental disability. If the hypothyroidism is not treated with replacement hormones, it can go on to cretinism and death."
The incidence of this particular deficiency, he observed, "is between rare and general. In certain populations it is more frequent, because it is a genetic disease." He added, "It is not necessarily associated with PAX-8, but the phenotype is similar.
"In the case of PAX-4," St.-Onge went on, "the phenotype resembles juvenile diabetes. Those knockout mice give us insight into the molecular mechanisms involved in diabetes, and also suggest gene therapy approaches."
German Project Invites Participants
After his PAX gene presentation, St.-Onge informed his listeners of an opportunity to take part in a major German genomics project.
"This is a very large-scale mutagenesis analysis of the mouse genome," St.-Onge began, "using as mutagen an alkylating chemical called ethylnitrosurea (ENU). It is tumorigenic, and currently the most powerful mutagen for the production of mutants in mice.
"The project's ultimate goal," he said, "is to generate 5,000 F1 mice in a recessive screen of 100 families, and 5,000 F3 animals per year."
The ENU-Mouse Mutagenesis Screen, he pointed out, is a subset project within Germany's participation in the Human Genome Project.
"It involves a collaboration between various institutes and the University of Munich. However," St.-Onge concluded, "it is open to other research groups that are not participants in the German Human Genome Project." (Send e-mail inquiries to email@example.com) *