On the C57BL/6J background Rab38^cht/Rab38^cht 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 Rab38^cht/Rab38^cht 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.)

Development

Rab38^cht 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.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Rab38^cht

Allele Symbol: Rab38^cht

Allele Name	chocolate
Allele Type	Spontaneous
Allele Synonym(s)	chocolate; cht
Gene Symbol and Name	Rab38, RAB38, member RAS oncogene family
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	7
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Rab38^cht related

Dermatology Research
- Color and White Spotting Defects
Cell Biology Research
- Vesicular Trafficking

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Rab38^cht/Rab38^cht
C57BL/6J-Rab38/J

integument phenotype

abnormal coat/hair pigmentation
- a rich dark brown coat is observed instead of a normal black coat
- dark brown coat color by weaning instead of non-agouti black of C57BL/6J strain

abnormal hair follicle melanogenesis
- a visible decrease in melanin levels is observed in hair follicles of the skin

abnormal skin pigmentation
- a lighter skin pigmentation is observed in the ear and tail
- lighter color pigmentation at birth compared to littermates

pigmentation phenotype

abnormal coat/hair pigmentation
- a rich dark brown coat is observed instead of a normal black coat
- dark brown coat color by weaning instead of non-agouti black of C57BL/6J strain

abnormal eye pigmentation
- lighter color pigmentation at birth compared to littermates

abnormal hair follicle melanogenesis
- a visible decrease in melanin levels is observed in hair follicles of the skin

abnormal iris pigmentation
- iris pigment exhibits mild transilluminations increasing peripherally

abnormal melanosome morphology
- melanocytes contain small, circular melanosomes with a brown hue that are distinct from the intensely black, oval melanosomes seen in control non-agout C57BL/6J mice

abnormal skin pigmentation
- a lighter skin pigmentation is observed in the ear and tail
- lighter color pigmentation at birth compared to littermates

decreased eye pigmentation
- a thinner pigment layer is observed in the retina and choroid

respiratory system phenotype

abnormal lung volume
- lung volume at 25 cmH2O airway pressure is significantly higher than that in wild-type mice
- significantly higher total lung volumes are observed at 12 and 24 weeks of age, as determined by water displacement

abnormal pulmonary acinus morphology
- Normal - however, no severe emphysematous changes or apparent signs of inflammation are observed
- the mean linear intercept, destructive index, and volume proportion of alveolar ducts and sacs are significantly increased at 24 weeks of age, indicating alveolar structural abnormalities

abnormal pulmonary alveolus wall morphology
- the volume proportion of the alveolar wall is significantly reduced at 12 and 24 weeks of age

abnormal surfactant secretion
- phosphatidylcholine and total phospholipid levels are increased in the lamellar body fraction and the lung homogenates, but no differences are seen in the BAL fluid
- surfactant protein B (SP-B) is increased in the lung homogenate but decreased in the BAL fluid

abnormal type II pneumocyte morphology
- at 18 weeks of age, alveolar type II cells are enlarged and contain lamellar bodies of increased size in larger numbers
- Normal - however, no differences in either alveolar type II cells or lamellar bodies are noted at E17

dilated pulmonary alveolar ducts
- at 24 weeks of age

dilated respiratory conducting tubes
- enlarged lower respiratory tract airspaces are observed at 12 and 24 weeks of age

enlarged alveolar lamellar bodies
- adult lamellar bodies are engorged with surfactant
- at 18 weeks of age, the size of lamellar bodies is significantly increased

increased alveolar lamellar body number
- at 18 weeks of age, the number of lamellar bodies is significantly increased

increased lung compliance
- Normal - airway opening pressure and the hysteresis ratio remain normal
- Normal - however, specific lung compliance (i.e. static lung compliance divided by the lung volume at 25 cmH2O airway pressure) is not significantly altered
- static lung compliance is significantly higher than that in wild-type mice

vision/eye phenotype

abnormal eye pigmentation
- lighter color pigmentation at birth compared to littermates

abnormal iris pigmentation
- iris pigment exhibits mild transilluminations increasing peripherally

decreased eye pigmentation
- a thinner pigment layer is observed in the retina and choroid

mammalian phenotype

hematopoietic system phenotype
- Normal - no defects in platelet function are detected
- no hematopoietic system abnormalities detected

homeostasis/metabolism phenotype
- Normal - normal bleeding times are observed at 12 weeks of age

References

Additional References

Potter MD; Rinchik EM. 1993. Deletion mapping of the chocolate (cht) locus within the Fes-Hbb region of mouse chromosome 7. Mamm Genome 4(1):46-8PubMed: 8422502 MGI: J:3753

Additional - Rab38^cht related

Technical Support

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Citation
When using the chocolate mouse strain in a publication, please cite the originating article(s) and include JAX stock #000976 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Rab38<cht>

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Also Known As:chocolate

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