International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

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POSTER 92 - BEHAVIORAL ANALYSIS OF MICE THAT ARE DEFICIENT IN AP-3 OR IN MURINE HPS1

Mrs Eunju Seong
University of Michigan
Mental Health Research Institute
University of Michigan
205 Zina Pitcher Place
Ann Arbor, MI 48109-0720
USA

Co-Authors: Burmeister M
Institutions: Mental Health Research Institute, University of Michigan

Hermansky Pudlak syndrome (HPS), a disorder characterized by hypopigmentation and delayed blood clotting, is explained by the inability of melanosomes, lysosomes, and storage granules of platelets to store their contents. Several years ago, in both HPS patients and the mouse mutant pale ear (ep), responsible mutations were found in a novel gene of unknown function, called HPS1. Recently, mutations in HPS patients and another mouse mutant were also identified in a gene encoding a subunit of the adaptor-like complex AP-3. The fact that AP-3 is involved in vesicle trafficking from the trans-Golgi network to endosomal compartments and a subset of synaptic vesicles explains well the cellular defects of HPS patients. Based on these findings, we hypothesized that the HPS protein is involved in the biological pathways of AP-3 and tested this hypothesis by constructing a mouse double mutant for HPS1 and AP-3. In the double mutant line, the introduction of ep mutation, which by itself only affects tail and ear pigmentation, significantly diluted the coat color of the AP-3 mouse mutant, supporting the given hypothesis. On the other hand, neither the HPS patients nor the ep mice have ever been reported to have neurological or behavioral abnormalities. However, here we report that in the open field test the double mutant mice displayed a synergistic increase in turning bias compared to each single mutant line, suggesting a neurological role of the HPS1 protein.