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.)
Rab38cht is a recessive mutation that arose spontaneously at The Jackson Laboratory in 1984 on the C57BL/6J background then at F140. Embryos from C57BL/6J females bred to homozygous chocolate males were frozen in 1987.
|Allele Synonym(s)||chocolate; cht|
|Gene Symbol and Name||Rab38, RAB38, member RAS oncogene family|
|Strain of Origin||C57BL/6J|
|General Note||This allele has been maintained on the C57BL/6J background at The Jackson Laboratory since 1984 when it was first identified.|
|Molecular Note||A G-to-T transversion mutation at coding nucleotide 56 (c.56G>T) in exon 1 results in a glycine to valine substitution in codon 19 of the gene (p.G19V). This mutation lies within the highly conserved phosphate/Mg2+ domain.|
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.