Hydrocephalus and the Accidental Transgene
A chat in an elevator at the National Institute of Environmental Health Sciences led to the discovery of a protein possibly linked to early brain development. Darryl C. Zeldin mentioned to an NIEHS colleague that a line of transgenic mice created by researchers studying the role of the CYP2J2 enzyme in heart function had developed swollen heads. As young adults the mice experienced rapid neurological decline. Zeldin explains, "In our mice, [CYP2J2] is expressed only in the heart." Therefore, he says, brain damage was likely linked to the location of the transgene insertion in the genome.
Zeldin's colleague, Perry Blackshear, director of the NIEHS Office of Clinical Research, discovered that the transgene interrupted the murine RXF4 locus, preventing expression of a novel transcript that his team named RFX4_v3.1
RFX4_v3 proved crucial for normal murine brain development. Disrupting a single copy of the gene prevented formation ...
