International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

TUESDAY OCTOBER 19

5.15pm – 5.30pm

A MOUSE INSERTIONAL MUTATION ON CHROMOSOME 9 CAUSES JUVENILE HYDROCEPHALUS

Schmidt JV, Kalinina EA, Steshina E

University of Illinois at Chicago, Chicago, IL, United States

A series of transgenic mouse lines were generated in our laboratory that carried a minimal promoter driving the lacZ reporter gene.  These transgenes functioned as enhancer traps, expressing lacZ under the control of enhancers located at their individual integration sites.  One transgenic line demonstrated expression in the epiphysis of the diencephalon at midgestation, a tissue that represents the rudiment of the developing pineal gland.  The mammalian pineal is an enigmatic tissue, potentially involved in such functions as circadian rhythms, reproduction and aging.  Hoping to identify the “trapped” gene expressed in the developing pineal, we used anchored PCR to localize the transgene integration to mouse chromosome 9.

Upon generation of homozygous transgenic animals, this line displayed a lethal juvenile hydrocephalus phenotype.  Visible hydrocephalus appears by 3-4 weeks of age, and progresses to death by 6-8 weeks.  This phenotype indicates that, in addition to trapping a gene involved in pineal development, the transgene also disrupted expression of a gene required for normal brain development.  It is not yet known if these two genes are the same, and candidate genes near the transgene insertion are being tested for a possible role.  Histological analysis is being used to further analyze expression of the transgene, as well as to visualize the alterations in brain morphology.  Identification of the trapped gene will allow us to study its role in pineal development and may identify a new mechanism for juvenile hydrocephalus.

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