Phenotypes Associated with This Genotype

Genotype
MGI:3588035

• Allelic Composition: Bloc1s6^pa/Bloc1s6^pa
• Genetic Background: B6.Cg-Bloc1s6^pa/J

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

mortality/aging

premature death ( J:53228 )

• survival beyond 16 months of age reduced to about 40%

pigmentation

diluted coat color ( J:99881 )

• display a generalized pigmented dilution

ocular albinism ( J:141035 )

• near total iris albinism

abnormal melanosome morphology ( J:80751 )

• immature melanosomes found in follicular melanocytes

• increased numbers of multivesicular forms

• striated forms more frequent as well but are usually misshapen and with irregular pigment

• do not increase in size with maturation

respiratory system

abnormal lung morphology ( J:4098 , J:53228 )

• at 8 months of age loss of endothelial cells accompanied by the presence of cellular debris in the alveolar spaces is seen (J:4098)

• by 12 months of age changes in lung morphology become more severe (J:4098)

• prior to 8 months of age no abnormalities are detected in the lung (J:4098)

• "honeycomb" effect on lung architecture (J:53228)

pulmonary edema ( J:4098 )

• at 12 months of age edema is seen in patches of the interstitium

abnormal lung interstitium morphology ( J:4098 )

• at 8 months of age the interstitial matrix appears disorganized due to the presence of cytoplasmic remnants in the alveolar interstitium

• at 12 months of age large lipid droplets and edema are seen in patches of the interstitium

abnormal pulmonary alveolus morphology ( J:4098 , J:88021 )

• cellular debris in the alveolar spaces is seen in mice at 8 months of age (J:4098)

• at 12 and 24 months of age some lungs show a few patchy areas of air space enlargement accompanied by alveolar septal destruction (J:4098)

• by 16 months of age, enlarged airspaces and destruction of alveolar tissue (J:88021)

abnormal pulmonary alveolus epithelium morphology ( J:4098 )

• at 8 months of age loss of epithelial cells accompanied by the presence of cellular debris in the alveolar spaces is seen

abnormal respiratory system physiology ( J:4098 )

• lung elastin levels are significantly reduced compared to controls

lung inflammation ( J:4098 )

• at 24 months of age lungs that don't display air space enlargement have scattered intraalveolar infiltration of inflammatory cells

emphysema ( J:4098 )

• emphysematous lesions are seen beginning at 12 months of age

abnormal lung volume ( J:4098 )

• lung volume is decreased at 8 months of age but increased at 12 and 28 months of age relative to age matched controls

abnormal respiratory mechanics ( J:88021 )

• lung reactance values decrease with age relative to controls

homeostasis/metabolism

decreased platelet ATP level ( J:7327 )

• platelet ATP levels are about half that of C57BL/6J controls

decreased platelet serotonin level ( J:7327 )

• platetelet serotonin levels less than 1% of normal

abnormal blood homeostasis ( J:4098 )

• serum elastase inhibitory capacity and alpha1-antitrypsin levels are significantly reduced compared to controls

abnormal platelet physiology ( J:221384 )

abnormal platelet activation ( J:7327 , J:221384 )

• reduced serotonin release after thrombin activation (J:7327)

• lysosomal enzyme secretion after thrombin activation about half normal (J:7327)

• platelets show impaired alpha granule content release in response to low-dose thrombin stimulation (J:221384)

• agonist-dependent lysosome release in platelets is impaired (J:221384)

• stimulation with a low dose of thrombin elicits a muted release of lysosomal enzymes from platelets (J:221384)

decreased platelet aggregation ( J:221384 )

• mice exhibit abnormal thrombus formation during laser-induced blood vessel damage, with total platelet accumulation severely attenuated by nearly 80%

increased bleeding time ( J:7327 )

• greater than 15 minutes

pulmonary edema ( J:4098 )

• at 12 months of age edema is seen in patches of the interstitium

abnormal urine enzyme level ( J:6219 )

• reduced secretion of lysosomal enzymes into the urine of testosterone treated mice

renal/urinary system

abnormal urine enzyme level ( J:6219 )

• reduced secretion of lysosomal enzymes into the urine of testosterone treated mice

abnormal kidney physiology ( J:6219 )

• kidney beta-glucuronidase levels increased 2.5X

• kidney levels of beta-galactosidase and alpha-mannosidase increased

• increased rate of lysosomal enzyme synthesis in kidneys

behavior/neurological

ataxia ( J:5215 )

• exaggerated ataxia in some mice after a swim test

impaired balance ( J:5215 )

• sometimes seen to roll over at the end of a swim test

impaired swimming ( J:5215 , J:89392 )

• erratic swimming pattern in some mice with head tilt (J:5215)

• 55/99 mice unable to swim - related to absence of normal otoliths (J:5215)

head tilt ( J:5215 )

• seen in about 25% of homozygotes

tonic seizures ( J:5215 )

• momentary, in mice displaying head tilt when first placed in water for a swim test

hearing/vestibular/ear

abnormal otolith morphology ( J:5215 , J:89392 )

• variable presence of otoliths - from normal to complete absence (J:5215)

• otolith development improves by maternal feeding with increased levels of manganese during early gestation (J:5215)

abnormal linear vestibular evoked potential ( J:89392 )

• variable defects in latencies, amplitudes and thresholds of VESPs, dependent on amounts of otoconia present

• mice with absent otoconia show absent vestibular compound action potentials

hematopoietic system

decreased platelet ATP level ( J:7327 )

• platelet ATP levels are about half that of C57BL/6J controls

decreased platelet ADP level ( J:7327 )

• platelet ADP levels are a third to a half that of C57BL/6J controls

decreased platelet dense granule number ( J:7327 )

• fewer dense granules per platelet

decreased platelet serotonin level ( J:7327 )

• platetelet serotonin levels less than 1% of normal

abnormal NK cell physiology ( J:6801 )

• lower natural killer cell activity

abnormal platelet physiology ( J:221384 )

abnormal platelet activation ( J:7327 , J:221384 )

• reduced serotonin release after thrombin activation (J:7327)

• lysosomal enzyme secretion after thrombin activation about half normal (J:7327)

• platelets show impaired alpha granule content release in response to low-dose thrombin stimulation (J:221384)

• agonist-dependent lysosome release in platelets is impaired (J:221384)

• stimulation with a low dose of thrombin elicits a muted release of lysosomal enzymes from platelets (J:221384)

decreased platelet aggregation ( J:221384 )

• mice exhibit abnormal thrombus formation during laser-induced blood vessel damage, with total platelet accumulation severely attenuated by nearly 80%

nervous system

tonic seizures ( J:5215 )

• momentary, in mice displaying head tilt when first placed in water for a swim test

cellular

decreased platelet ATP level ( J:7327 )

• platelet ATP levels are about half that of C57BL/6J controls

abnormal lysosome physiology ( J:6801 )

• significant increase in lysosomal enzyme activity of beta-galactosidase and beta-glucuronidase, and to a lesser extent N-acetyl-beta-hexoseaminidase, in kidney extracts

immune system

abnormal NK cell physiology ( J:6801 )

• lower natural killer cell activity

lung inflammation ( J:4098 )

• at 24 months of age lungs that don't display air space enlargement have scattered intraalveolar infiltration of inflammatory cells

vision/eye

ocular albinism ( J:141035 )

• near total iris albinism

growth/size/body

increased body weight ( J:4098 )

• at 12 months of age but not at 8 or 28 months of age

integument

integument phenotype ( J:68448 )

N • electron microscopy of the skin shows regular collagen bundles and no excess collagen deposition

diluted coat color ( J:99881 )

• display a generalized pigmented dilution

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hermansky-Pudlak syndrome 9		DOID:0060547	OMIM:614171	J:221384
platelet storage pool deficiency		DOID:2223	OMIM:185050	J:7327
pulmonary emphysema		DOID:9675	OMIM:130700	J:4098