International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

B13. A Novel Imprinting Gene which Carries A Ring Finger Motif was Mutated in A Mutant Mouse Exhibiting Abnormal Osteogenesis and Poly-Cystic Kidney

Michiyo Ishida1, Shinji Sasaki1, Tomohito Itho1, Amy Chen2, Lissa Garrette2, Anthony Wynshaw-Boris3 and Shinji Hirotsune1
1Shirakawa Institute of Animal Genetics Odakura Nishigo Fukushima, Japan
2National Human Genome Research Institute NIH USA
3Department of Pediatrics UCSD USA

We identified a novel imprinting gene which carries a ring finger motif as a responsible gene of a mutant mouse exhibiting abnormal osteogenesis and poly-cystic kidney. We made this mutant mouse incidentally by insertional mutagenesis. Mutant mice will die within a couple of days due to severe failure of thrive. Survived mice are suffering from bone deformity due to incomplete mineralization and various degree of poly-cystic kidney. Although differentiation of osteoblast and osteoclast were grossly normal, mineral density in the bone was less than half. While transmission pattern suggested dominant phenotype, further genetic study indicated a responsible gene was imprinted by paternal expression. We mapped the transgenes at chromosome five by FISH and RH. Curiously, location was outside of imprinting region which was estimated by robertosonian translocation mice. In this region, transgenes were integrated by a head and head fashion accompanied with 8kbp deletion. In order to identify a mutation responsible gene, we sequenced BAC clones encompassing the critical region. Extensive genomic sequence indicated three transcription units are present within the critical region. Northern blot analysis demonstrated one gene which is carrying a ring finger motif was only imprinted and reduced in expression in the mutant. Thus, we concluded that a novel imprinting carrying a ring finger motif was a responsible gene of the phenotypes. This gene was highly expressed brain, kidney and testis. Now, we are elucidating a molecular mechanism how this gene links to the phenotypes.

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