Phenotypes Associated with This Genotype

Genotype
MGI:2663842

• Allelic Composition: Bloc1s4^cno/Bloc1s4^cno
• Genetic Background: C3H/HeJ-Bloc1s4^cno

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

pigmentation

diluted coat color ( J:61187 )

• agouti mice are khaki colored; nonagouti mice resemble homozygous pallid mice

• homozygotes display severe coat-color dilution

abnormal choroid pigmentation ( J:61187 )

• mutant melanosomes are reduced in number, smaller and less melanized than wild-type

abnormal retina pigmentation ( J:61187 )

• mutant melanosomes are reduced in number, smaller and less melanized than wild-type

abnormal melanosome morphology ( J:61187 )

• mutant melanosomes appear immature and are severely reduced in number in the eye and skin, resulting in severe oculocutaneous albinism

abnormal melanogenesis ( J:61187 )

• homozygotes display abnormal melanosome formation both quantitatively and qualitatively

hypopigmentation ( J:61187 )

• homozygotes display a severe reduction in skin and eye pigment relative to wild-type controls

decreased eye pigmentation ( J:61187 )

• mutant melanosomes are severely reduced in number throughout the retinal pigmented epithelium and choroid layers

hematopoietic system

decreased platelet ATP level ( J:61187 )

• platelet ATP release is undetectable

decreased platelet calcium level ( J:61187 )

• loss of dense body electron density suggests a low platelet Ca²⁺ content

decreased platelet dense granule number ( J:61187 )

• adult homozygotes show a 6-fold decrease in the number of dense bodies (delta granules) per platelet relative to wild-type controls

• most mutant platelets contain no visible dense bodies, although a small number have one or two

• in contrast, the number and size of alpha-granules remains normal

decreased platelet serotonin level ( J:61187 )

• mutant platelet serotonin levels are reduced to ~3% of wild-type levels

decreased platelet aggregation ( J:61187 )

• platelet aggregation determined in whole blood by the impedance method in response to collagen (1 or 4 ug/mL) is reduced

abnormal platelet dense granule physiology ( J:61187 )

• mutant platelets show a marked deficiency of dense body contents

homeostasis/metabolism

decreased platelet ATP level ( J:61187 )

• platelet ATP release is undetectable

decreased platelet calcium level ( J:61187 )

• loss of dense body electron density suggests a low platelet Ca²⁺ content

decreased platelet serotonin level ( J:61187 )

• mutant platelet serotonin levels are reduced to ~3% of wild-type levels

decreased platelet aggregation ( J:61187 )

• platelet aggregation determined in whole blood by the impedance method in response to collagen (1 or 4 ug/mL) is reduced

abnormal platelet dense granule physiology ( J:61187 )

• mutant platelets show a marked deficiency of dense body contents

increased bleeding time ( J:61187 )

• adult homozygotes exhibit significantly increased bleeding times relative to wild-type controls (15.9 +/- 2.9 min versus 1.5 +/- 0.6 min, respectively)

• however, all hematologic parameters, including WBC and RBC counts, hemoglobin, hematocrit, platelet counts and mean platelet volume, are normal

vision/eye

abnormal retina pigmentation ( J:61187 )

• mutant melanosomes are reduced in number, smaller and less melanized than wild-type

decreased eye pigmentation ( J:61187 )

• mutant melanosomes are severely reduced in number throughout the retinal pigmented epithelium and choroid layers

abnormal optic choroid morphology ( J:61187 )

• homozygotes display a marked reduction in the choroid layer relative to wild-type controls

abnormal choroid pigmentation ( J:61187 )

• mutant melanosomes are reduced in number, smaller and less melanized than wild-type

behavior/neurological

abnormal postural reflex ( J:61187 )

• ~75% of homozygotes exhibit abnormal postural and balance reflexes with variable severity, suggesting otolith defects

impaired balance ( J:61187 )

• others are unable to stand upright

• some homozygotes display balance deficits only upon handling and close observation

head tilt ( J:61187 )

• some homozygotes display abnormal head tilting only upon handling and close observation

• others exhibit extreme leaning to one side

renal/urinary system

abnormal kidney physiology ( J:61187 )

• 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

liver/biliary system

abnormal liver physiology ( J:61187 )

• in mutant livers, activity levels of alpha-galactosidase are increased by >2-fold relative to wild-type controls

cellular

decreased platelet ATP level ( J:61187 )

• platelet ATP release is undetectable

decreased lysosomal enzyme secretion ( J:61187 )

• homozygotes display a lysosomal secretion defect resulting in enzyme accumulation in the kidney and liver, but not spleen or platelets

• 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

abnormal vesicle-mediated transport ( J:83960 )

• failure of mutant CNO protein to coassemble with pallidin in cultured fibroblasts from homozygous mutant mice indicates that BLOC-1 (biogenesis of lysosome-related organelles complex-1) is disrupted

respiratory system

respiratory system phenotype ( J:61187 )

N • no gross pathologic abnormalities are detected in lung at 10 months of age

integument

diluted coat color ( J:61187 )

• agouti mice are khaki colored; nonagouti mice resemble homozygous pallid mice

• homozygotes display severe coat-color dilution

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hermansky-Pudlak syndrome		DOID:3753	OMIM:PS203300	J:61187