On the C57BL/6J background Rab38cht/Rab38cht mice have a rich dark chocolate coat color instead of the normal black coat. This can be difficult to distinguish, but is made easier by the lightened color in the ear pinnae and tail. At birth the eyes of Rab38cht/Rab38cht mice are lighter in color than wild type C57BL/6J mice. The melanosomes in melanocytes cultured from newborn C57BL/6J mice are oval and intensely black while those of chocolate mice are circular and brown. The end-stage melanosomes of chocolate mice contain less TYRP1 than do wild type mice. Mutations in Tyrp1 result in increased brown rather than black pigment. Thus, Loftus et al. have hypothesized that the chocolate mutation results in decreased black pigmentation because RAB38 is important in the vesicular trafficking that moves TYRP1 from the trans-Golgi network to the end-stage melanosome. Many of the pigment diluting mutations with defective organelle trafficking also have a platelet storage pool deficiency. However, chocolate mice do not have extended bleeding times. (Potter and Rinchik, 1993; MacPike and Mobraaten, 1984; Davisson and Bunker, 1986.) The RAB family of proteins is comprised of small GTP-binding proteins that transition between the cytoplasm and organelle membranes and are believed to regulate vesicle transport. In mouse the Rab38 gene encodes a transcript of 1.6 kb. The cDNA has a 636 base pair open reading frame predicted to encode a 211 amino acid protein with the 5 GTP-binding domains standard for members of the Ras superfamily. The two-cysteine carboxy terminal motif important for the binding of lipid moieties differs from the consensus sequence found in other RAB proteins and is more like that found in RAS proteins. The Rab38 sequence is highly conserved among mammals. Mouse Rab38 transcript is detected in melanocytes, melanoma cell lines, and at varying levels in many tissues including adrenal gland, uterus, testes, kidney, prostate, placenta, and others. Using in situ hybridization and immunohistochemistry, Rab38 localizes in rat lung tissue to alveolar corner cells, primarily alveolar type II cells, and bronchial epithelial cells, primarily terminal bronchial cells. Confocal microscopy and subcellular fractionation of cultured rat alveolar type II cells show that RAB38 is absent from the nucleus but is present in the cytoplasm and co-localizes with an endoplasmic reticulum marker, but not with markers for golgi, trans golgi network, or endosomes. A GFP-RAB38 fusion protein was found to co-localize with end-stage melanosomes in primary mouse melanocyte cultures. (Jager et al., 2000; Osanai et al., 2001; Loftus et al., 2002.) The chocolate allele of Rab38 has a G to T transversion at nucleotide146 in exon 1. This translates as a glycine to valine substitution at amino acid 19. Three dimensional modeling predicts that this residue directly contacts GTP in the nucleotide binding pocket. A PCR protocol to identify this allele has been developed. (Loftus et al., 2002.)

These mice carry a spontaneous mutation at the Rab38 locus characterized by rich dark chocolate coat color.

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

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