Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.C3-Cnocno/LlpJ    (Changed: 17-AUG-12 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse

Description
Mice homozygous for the cappuccino mutation have a severe dilution in coat color and diminished eye pigmentation. The BLOC-1 complex is disrupted and melanosome development appears arrested at an early stage. These homozygotes have significantly increased bleed times due to defective platelet aggregation. This mutation provides a model for Hermansky-Pudlak Syndrome.

Development
The cappuccino mutation arose spontaneously in the C3H/HeJ inbred strain at The Jackson Laboratory. This mutation was backcrossed onto the C57BL/6J background for at least 10 backcross generations in the laboratory of Luanne Peters and sperm from homozygous males was cryopreserved in 2010.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Bloc1s4^cno/Bloc1s4^cno

        C3H/HeJ

• pigmentation phenotype
• abnormal choroid pigmentation
  • mutant melanosomes are reduced in number, smaller and less melanized than wild-type   (MGI Ref ID J:61187)
• abnormal melanogenesis
  • homozygotes display abnormal melanosome formation both quantitatively and qualitatively   (MGI Ref ID J:61187)
• abnormal melanosome morphology
  • mutant melanosomes appear immature and are severely reduced in number in the eye and skin, resulting in severe oculocutaneous albinism   (MGI Ref ID J:61187)
• abnormal retinal pigmentation
  • mutant melanosomes are reduced in number, smaller and less melanized than wild-type   (MGI Ref ID J:61187)
• diluted coat color
  • agouti mice are khaki colored; nonagouti mice resemble homozygous pallid mice   (MGI Ref ID J:61187)
  • homozygotes display severe coat-color dilution   (MGI Ref ID J:61187)
• hypopigmentation
  • homozygotes display a severe reduction in skin and eye pigment relative to wild-type controls   (MGI Ref ID J:61187)
• • decreased eye pigmentation
    • mutant melanosomes are severely reduced in number throughout the retinal pigmented epithelium and choroid layers   (MGI Ref ID J:61187)
• hematopoietic system phenotype
• abnormal platelet dense granule number
  • adult homozygotes show a 6-fold decrease in the number of dense bodies (delta granules) per platelet relative to wild-type controls   (MGI Ref ID J:61187)
  • most mutant platelets contain no visible dense bodies, although a small number have one or two   (MGI Ref ID J:61187)
  • in contrast, the number and size of alpha-granules remains normal   (MGI Ref ID J:61187)
• abnormal platelet dense granule physiology
  • mutant platelets show a marked deficiency of dense body contents   (MGI Ref ID J:61187)
• decreased platelet ATP level
  • platelet ATP release is undetectable   (MGI Ref ID J:61187)
• decreased platelet aggregation
  • platelet aggregation determined in whole blood by the impedance method in response to collagen (1 or 4 ug/mL) is reduced   (MGI Ref ID J:61187)
• decreased platelet calcium level
  • loss of dense body electron density suggests a low platelet Ca²⁺ content   (MGI Ref ID J:61187)
• decreased platelet serotonin level
  • mutant platelet serotonin levels are reduced to ~3% of wild-type levels   (MGI Ref ID J:61187)
• homeostasis/metabolism phenotype
• abnormal platelet dense granule physiology
  • mutant platelets show a marked deficiency of dense body contents   (MGI Ref ID J:61187)
• decreased platelet aggregation
  • platelet aggregation determined in whole blood by the impedance method in response to collagen (1 or 4 ug/mL) is reduced   (MGI Ref ID J:61187)
• decreased platelet calcium level
  • loss of dense body electron density suggests a low platelet Ca²⁺ content   (MGI Ref ID J:61187)
• decreased platelet serotonin level
  • mutant platelet serotonin levels are reduced to ~3% of wild-type levels   (MGI Ref ID J:61187)
• increased bleeding time
  • adult homozygotes exhibit significantly increased bleeding times relative to wild-type controls (15.9 +/- 2.9 min versus 1.5 +/- 0.6 min, respectively)   (MGI Ref ID J:61187)
  • however, all hematologic parameters, including WBC and RBC counts, hemoglobin, hematocrit, platelet counts and mean platelet volume, are normal   (MGI Ref ID J:61187)
• vision/eye phenotype
• abnormal choroid morphology
  • homozygotes display a marked reduction in the choroid layer relative to wild-type controls   (MGI Ref ID J:61187)
• • abnormal choroid pigmentation
    • mutant melanosomes are reduced in number, smaller and less melanized than wild-type   (MGI Ref ID J:61187)
• abnormal retinal pigmentation
  • mutant melanosomes are reduced in number, smaller and less melanized than wild-type   (MGI Ref ID J:61187)
• decreased eye pigmentation
  • mutant melanosomes are severely reduced in number throughout the retinal pigmented epithelium and choroid layers   (MGI Ref ID J:61187)
• behavior/neurological phenotype
• abnormal postural reflex
  • ~75% of homozygotes exhibit abnormal postural and balance reflexes with variable severity, suggesting otolith defects   (MGI Ref ID J:61187)
• head tilt
  • some homozygotes display abnormal head tilting only upon handling and close observation   (MGI Ref ID J:61187)
  • others exhibit extreme leaning to one side   (MGI Ref ID J:61187)
• impaired balance
  • some homozygotes display balance deficits only upon handling and close observation   (MGI Ref ID J:61187)
  • others are unable to stand upright   (MGI Ref ID J:61187)
• renal/urinary system phenotype
• abnormal kidney physiology
  • in mutant kidneys, activity levels of beta-galactosidase, beta-glucuronidase and alpha-galactosidase are increased by 2.0- to 2.5-fold relative to wild-type controls   (MGI Ref ID J:61187)
• liver/biliary system phenotype
• abnormal liver physiology
  • in mutant livers, activity levels of alpha-galactosidase are increased by >2-fold relative to wild-type controls   (MGI Ref ID J:61187)
• cellular phenotype
• abnormal vesicle-mediated transport
  • reduced levels of pallidin and muted indicate that BLOC-1 (biogenesis of lysosome-related organelles complex-1) is disrupted   (MGI Ref ID J:83960)
• decreased lysosomal enzyme secretion
  • homozygotes display a lysosomal secretion defect resulting in enzyme accumulation in the kidney and liver, but not spleen or platelets   (MGI Ref ID J:61187)
  • however, lysosomal protein trafficking studies indicate that the cellular distribution of AP-3 proteins and internalization of lysosomal-associated membrane protein 1(LAMP1) is normal in mutant fibroblasts   (MGI Ref ID J:61187)
• respiratory system phenotype
• *normal* respiratory system phenotype
  • no gross pathologic abnormalities are detected in lung at 10 months of age   (MGI Ref ID J:61187)
• integument phenotype
• diluted coat color
  • agouti mice are khaki colored; nonagouti mice resemble homozygous pallid mice   (MGI Ref ID J:61187)
  • homozygotes display severe coat-color dilution   (MGI Ref ID J:61187)

Bloc1s4^cno/Bloc1s4^cno

        involves: C3H/HeJ

• pigmentation phenotype
• abnormal melanosome morphology
  • smaller and abnormal melanosomes   (MGI Ref ID J:80751)
  • pigmentation appears granular and irregulary deposited   (MGI Ref ID J:80751)
  • increase in the percentage of both multivesicular and type II/III melanosome forms (immature forms) and a relative lack of elliptical type IV forms   (MGI Ref ID J:80751)
  • progression in size from precursor (type II/III) to mature (type IV) melanosome is abolished, suggesting that melanosome development is arrested at an early stage   (MGI Ref ID J:80751)

View Research Applications

Research Applications

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

Bloc1s4^cno related

Cell Biology Research
Vesicular Trafficking

Dermatology Research
Color and White Spotting Defects

Hematological Research
Clotting Defects
Platelet Defects
      Alterations in platelet aggregation
      platelet storage pool deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bloc1s4cno
Allele Name		cappuccino
Allele Type		Spontaneous
Strain of Origin		C3H/HeJ
Gene Symbol and Name		Bloc1s4, biogenesis of organelles complex-1, subunit 4, cappuccino
Chromosome		5
Gene Common Name(s)		2610101N07Rik; BCAS4L; BLOS4; CNO; Cno; RGD1306037; RIKEN cDNA 2610101N07 gene; cappuccino;
General Note		Phenotypic Similarity to Human Syndrome: Hermansky-Pudlak Syndrome (J:80751, J:61187)
Molecular Note		This allele comprises an 11 bp deletion that causes a frame shift that alters the C-terminal one third of the protein sequence. Expression and subcellular localization of the protein are not affected by this mutation. The mutation does affect the ability of the protein to form a complex with other lysosomal related proteins. [MGI Ref ID J:83960]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Gwynn B; Ciciotte SL; Hunter SJ; Washburn LL; Smith RS; Andersen SG; Swank RT; Dell'Angelica EC; Bonifacino JS; Eicher EM; Peters LL. 2000. Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism. Blood 96(13):4227-35. [PubMed: 11110696]  [MGI Ref ID J:61187]

Nguyen T; Novak EK; Kermani M; Fluhr J; Peters LL; Swank RT; Wei ML. 2002. Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development. J Invest Dermatol 119(5):1156-64. [PubMed: 12445206]  [MGI Ref ID J:80751]

Additional References

Bloc1s4^cno related

Ciciotte SL; Gwynn B; Moriyama K; Huizing M; Gahl WA; Bonifacino JS; Peters LL. 2003. Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1). Blood 101(11):4402-7. [PubMed: 12576321]  [MGI Ref ID J:83960]

Newell-Litwa K; Chintala S; Jenkins S; Pare JF; McGaha L; Smith Y; Faundez V. 2010. Hermansky-Pudlak protein complexes, AP-3 and BLOC-1, differentially regulate presynaptic composition in the striatum and hippocampus. J Neurosci 30(3):820-31. [PubMed: 20089890]  [MGI Ref ID J:157701]

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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