International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 81 - FRINGE GENE EXPRESSION IN THE DEVELOPING MOUSE LIVER

Dr. Kathleen Loomes
The Children's Hospital of Philadelphia
34th St. and Civic Center Blvd.
Philadelphia, PA 19104
USA

Co-Authors: 2) Taichman DB, 1) Glover CL, 3) Baldwin HS, 4) Oakey RJ
Institutions: 2)Division of Pulmonary Medicine, University of Pennsylvania School of Medicine. 1)Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia. 3)Division of Cardiology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine. 4)Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine

The discovery that Jag1 is the disease gene for Alagille syndrome (AGS), a developmental disorder with bile duct paucity as a major feature, implicates Jag1 and the Notch signaling pathway in bile duct development. The Fringe genes, Manic fringe (Mfng), Lunatic fringe (Lfng) and Radical fringe (Rfng), directly modify Notch and affect its ability to respond to signaling by a ligand. We hypothesize that the Fringe genes, as modifiers of the Notch pathway, play an important role in liver and bile duct development.  RNA and cDNA were prepared from staged mouse livers ranging from 11.5 dpc to 12 weeks postnatal. Gene expression was analyzed using real time quantitative RT-PCR. All reactions were performed in multiplex with GAPDH. Lfng expression is low relative to GAPDH at 11.5 dpc, gradually increasing to a peak of 5 times the initial value at 13.5 dpc, and then falling by 18.5 dpc. Similarly, Rfng expression peaks at 13.5 dpc at about 2.5 times the initial value. In contrast, Mfng expression remains relatively constant throughout development and then peaks postnatally at 12 weeks at 5 times the initial value. Each fringe gene demonstrates a unique pattern of expression in the developing liver when measured by real time quantitative RT-PCR. Lfng and Rfng expression both peak at 13.5 dpc, just prior to the onset of bile duct development.  Studies are ongoing to define fringe expression spatially in the liver and to analyze the fringe knockout mice for any liver abnormalities.


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