THE ROLE OF MURINE AIM1 IN NEURAL CREST/MELANOCYTE DEVELOPMENT

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AIM1 was identified in a substractive hybridization experiment that selected for cDNAs that are absent in melanoma (AIM). AIM1 is not expressed in a human tumorigenic melanoma cell line (UACC- 903) yet highly expressed in a non-tumorogenic melanoma cell line suppressed by introduction of human chromosome 6 (MCH- 361C1). We are developing a mouse model system to study the role of AIM1 in melanoma biology and normal melanocyte development. The mouse homologue of AIM1, muAIM1, was isolated from an adult liver cDNA library using the GeneTrapper (LTI) method. Comparison of the nucleic acid sequences and deduced open reading frame demonstrated over 85% identity in restricted areas of the gene. Sequence database searches identified regions of AIM1 with similarity to beta, gamma-crystallin family, flanked by regions of AIM1 with no obvious similarity to other proteins. The location of muAIM1 in the mouse genome was examined by PCR- RFLP using the Jackson laboratory backcross panel and found to reside on proximal mouse chromsome 10; a region syntenic to human chromsome 6. To further investigate the role of AIM1 in melanocyte development and malignant transformation, RT-PCR, Northern blot and in situ hybridization analyses were used to determine the expression pattern of muAIM1 in adult mouse tissues and during embryonic development. Correlation with the developing hair follicle was the most striking developmental feature.