International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 35 - MOLECULAR AND GENETIC ANALYSIS OF THE MOUSE HOMOLOGUE OF A NOVEL ZEBRAFISH NEUROGENIC MUTATION

R Rajendra
Molecular Genetics and Microbiology

Wu J, Artzt K
University of Texas at Austin

We are analyzing a gene that was identified originally in zebrafish in a retroviral insertional mutant screen done in the Hopkins lab (M.I.T. Cancer Center). This mutant, Hi904, is an allele of the zebrafish mutant mind bomb (mib). It is a homozygous recessive lethal on day 5 of development and has a phenotype that is detectable at 33 hours post fertilization. Progressive temporal disorganization of the neural epithelium is observed. Histological analysis reveals that the neuro-epithelium develops normally initially but later loses its architecture and rounded cells start to fill the brain cavity. This pattern appears to be typical of a neural tumor that occurs in young children. Homology searches have revealed that this gene is highly conserved from Drosophila onwards. The mouse gene, referred to as mib1, maps to chromosome 18 at 3.0 cM. mib1 spans almost 91 Kb coding for a 10 Kb transcript which translates into an ~110 kDa protein. A mouse knockout of mib1 is being generated. The expression pattern of mib1 that is being characterized using in situ hybridization, has been found mainly in the neuro-epithelium at E 8.5. The mib1 protein sequence shows the presence of a ZZ finger domain, 8 ankyrin repeats, 3 RING finger domains and 2 copies of a novel domain. The presence of the RING finger domains indicates a possible role as a ubiquitin E3 ligase. Biochemical studies are in progress to determine its function.


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