The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a.

@article{citeulike:2984721, abstract = {Exon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a). The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes.}, address = {Department of Human Genetics, 4708 Medical Science II, University of Michigan, Ann Arbor, MI 48109-0618, USA.}, author = {Jones, J. M. and Huang, J. D. and Mermall, V. and Hamilton, B. A. and Mooseker, M. S. and Escayg, A. and Copeland, N. G. and Jenkins, N. A. and Meisler, M. H. }, citeulike-article-id = {2984721}, issn = {0964-6906}, journal = {Human molecular genetics}, keywords = {dendritic-compartment, dendritic-mrna, mir, myo5a, neuron}, month = {March}, number = {5}, pages = {821--828}, posted-at = {2008-07-10 12:52:52}, priority = {2}, title = {The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10749990}, volume = {9}, year = {2000} }

TY - JOUR ID - citeulike:2984721 L3 - citeulike-article-id:2984721 TI - The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a. JF - Human molecular genetics VL - 9 IS - 5 SP - 821 EP - 828 AD - Department of Human Genetics, 4708 Medical Science II, University of Michigan, Ann Arbor, MI 48109-0618, USA. SN - 0964-6906 N2 - Exon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a). The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes. KW - dendritic-compartment KW - dendritic-mrna KW - mir KW - myo5a KW - neuron AU - Jones, JM AU - Huang, JD AU - Mermall, V AU - Hamilton, BA AU - Mooseker, MS AU - Escayg, A AU - Copeland, NG AU - Jenkins, NA AU - Meisler, MH PY - 2000/03/22/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10749990 ER -