Phenotypes Associated with This Genotype

Genotype
MGI:3702286

• Allelic Composition: Ap3b1^pe/Ap3b1^pe
• Genetic Background: B6.C3-Ap3b1^pe/J

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

mortality/aging

premature death ( J:53228 )

• about 40% survive less than 2 years

vision/eye

abnormal eye movement ( J:12089 )

• absence of optokinetic nystagmus

abnormal vision ( J:12089 )

• visual sensitivity is diminished on dim backgrounds but sensitivity is normal on bright backgrounds

nervous system

abnormal optic tract morphology ( J:29747 )

• inferior fasciculus of the accessory optic tract is significantly reduced

abnormal midbrain roof plate morphology ( J:29747 )

• denser optic projections to the contralateral anterior and posterior olivary pretectal nuclei

• projections to the rostral ipsilateral anterior olivary pretectal nucleus are reduced in density

• accessory input to the contralateral dorsal terminal nucleus is substantially reduced

abnormal superior colliculus morphology ( J:12089 )

• reduced ipsilateral projections to the superior colliculus

abnormal forebrain morphology ( J:12089 )

abnormal lateral geniculate nucleus morphology ( J:12089 )

• reduced ipsilateral optic projections

abnormal visual cortex morphology ( J:12089 )

• reduced ipsilateral projections to the visual cortex

respiratory system

lung hemorrhage ( J:53228 )

• in about 3/8 of homozygotes surviving more than 2 years

abnormal pulmonary alveolus morphology ( J:53228 )

• lungs show a moderately honeycombed structure

overexpanded pulmonary alveolus ( J:53228 )

• moderate airspace enlargement

cardiovascular system

lung hemorrhage ( J:53228 )

• in about 3/8 of homozygotes surviving more than 2 years

behavior/neurological

abnormal eye movement ( J:12089 )

• absence of optokinetic nystagmus

homeostasis/metabolism

decreased platelet ATP level ( J:7327 )

• platelet ATP levels are much lower than in C57BL/6J controls

decreased platelet serotonin level ( J:7327 )

• less than 3% of normal platelet serotonin levels

abnormal platelet activation ( J:221384 )

• platelets show impaired alpha granule content release in response to low-dose thrombin stimulation

• agonist-dependent lysosome release in platelets is impaired

• stimulation with a low dose of thrombin elicits a mutated release of lysosomal enzymes from platelets

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 )

• bleed time averaging over 15 minutes after tail nick is much greater than the 3.8 minutes for C57BL/6J controls

abnormal enzyme/coenzyme activity ( J:221384 )

• the activity of beta-glucuronidase, a lysosomal enzyme, is reduced by 28% in platelets

hematopoietic system

abnormal platelet dense granule morphology ( J:152219 )

• transmission electron microscopy of platelets shows that the dense granules have very little contents, although no other subcellular platelet abnormalities are found

decreased platelet ATP level ( J:7327 )

• platelet ATP levels are much lower than in C57BL/6J controls

decreased platelet ADP level ( J:7327 )

• platelet ADP levels are much lower than in C57BL/6J controls

decreased platelet dense granule number ( J:7327 )

• vastly reduced number of platelet dense granules

decreased platelet serotonin level ( J:7327 )

• less than 3% of normal platelet serotonin levels

abnormal platelet activation ( J:221384 )

• platelets show impaired alpha granule content release in response to low-dose thrombin stimulation

• agonist-dependent lysosome release in platelets is impaired

• stimulation with a low dose of thrombin elicits a mutated release of lysosomal enzymes from platelets

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%

cellular

decreased platelet ATP level ( J:7327 )

• platelet ATP levels are much lower than in C57BL/6J controls

abnormal lysosome morphology ( J:152219 )

• in primary macrophages and melanocyte derived cell lines of pearl mutants immunohistochemistry staining the delta subunit of the AP3 complex reveals a weak, diffuse cytoplasmic staining rather than the normal punctate pattern

accumulation of giant lysosomes in kidney/renal tubule cells ( J:152219 )

• transmission electron microscopy shows numerous enlarged lysosomes in the kidney proximal tubule cells

decreased lysosomal enzyme secretion ( J:7327 )

• thrombin stimulation of platelets results in slightly more than half the normal levels of secretion of beta-glucuronidase and beta-galactosidase

renal/urinary system

accumulation of giant lysosomes in kidney/renal tubule cells ( J:152219 )

• transmission electron microscopy shows numerous enlarged lysosomes in the kidney proximal tubule cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hermansky-Pudlak syndrome 2		DOID:0060540	OMIM:608233	J:221384
platelet storage pool deficiency		DOID:2223	OMIM:185050	J:7327