International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 77 - AN INSERTION OF A RETROTRANSPOSON IN THE EDNRB GENE CAUSES PIEBALD COAT COLOR OF THE S/S MOUSE

Ohtani S 1, Yamada T 2, Sakurai T 2, Tsuji T 1, Yanagisawa M 2, Kunieda T 1

1 Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan, 2 Howard Hughes Medical Institute, Department of Molecular Genetics University of Texas Southwestern Medical Center, Dallas, United States

JF1/Msf is an inbred mouse strain originated from Japanese fancy mice and shows piebald coat color controlled by s, a recessive allele of endothelin-B receptor (Ednrb) gene. The Ednrb gene plays an important role in differentiation and migration of neural crest cells including melanocytes and ganglion cells and the loss of function of the Ednrb gene cause abnormal coat color, megacolon, and sensorineural deafness. The expression level of this gene is significantly decreased in the s/s mice, but the exact mutation in the Ednrb gene of s allele has not yet been identified. We, therefore, analyzed the nucleotide sequences of the Ednrb gene in JF1/Msf mouse to reveal the causative mutation of the s allele. Southern blot analysis showed an approximately 5-kb insertion in the first intron of the gene. Sequencing analysis of this region revealed that the inserted sequence shows similarity with mouse ETn (Early retrotransposon). Comparison of the transcripts of the gene between wild-type and s/s mice revealed that the insertion of the retrotransposon results in abnormal transcripts caused by a cryptic splicing between the first exon and the inserted retrotransposon, and the decreased expression of the normal transcripts. We concluded that the piebald phenotype of the s/s mouse is caused by the insertion of ETn-like retrotransposon in the first intron of the Ednrb gene.

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