Phenotypes associated with this allele

• Allele Symbol: Ap3b1^pe
• Allele Name: pearl
• Allele ID: MGI:1856989
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ap3b1^pe/Ap3b1^pe	B6.C3-Ap3b1^pe/J	MGI:3702286
hm2	Ap3b1^pe/Ap3b1^pe	involves: C3H/He	MGI:2655702
hm3	Ap3b1^pe/Ap3b1^pe	involves: C3H/He * C57BL/6J	MGI:3702282
ht4	Ap3b1^pe/Ap3b1^pe-6J	(B6.C3-Ap3b1^pe x C3H/HeJ-Ap3b1^pe-6J)F1	MGI:5315726
ht5	Ap3b1^pe/Ap3b1^pe-9J	(B6.C3-Ap3b1^pe x C57BL/6J-Ap3b1^pe-9J)F1	MGI:5315768
cx6	Ap3b1^pe/Ap3b1^pe Hps1^ep/Hps1^ep	involves: C3H/He * C3HeB/FeJ * C57BL/6J	MGI:3586968

Genotype
MGI:3702286

hm1

• 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

Genotype
MGI:2655702

hm2

• Allelic Composition: Ap3b1^pe/Ap3b1^pe
• Genetic Background: involves: C3H/He

mortality/aging

pregnancy-related premature death ( J:15331 )

• females tend to die during pregnancy and while nursing

neonatal lethality, incomplete penetrance ( J:15331 )

• smaller litter sizes at birth

postnatal lethality ( J:15331 )

• reduced litter sizes at weaning

pigmentation

abnormal coat/hair pigmentation ( J:6739 , J:15331 )

• about 6% of homozygotes have normal color patches (J:6739)

• if more than 5% of coat is normally pigmented then germinal reversion is also seen (J:6739)

diluted coat color ( J:15331 )

• greatest at the base of hairs but affecting the whole hair

• snout, ears, feet and tail particularly lighter than controls

• the characteristic yellowish mask around the eyes is diluted to near-white

white spotting ( J:15331 )

• white "mask" around eyes

• a long, narrow mid ventral white streak is occasionally observed

decreased eye pigmentation ( J:15331 )

• at birth but normal in adults

abnormal melanosome morphology ( J:80751 )

• immature melanosome forms (type II/III) accumulate to a certain degree but fully mature forms are also observed

• increase in membrane blebbing on type IV melanosomes, suggesting abnormal vesicular trafficking

homeostasis/metabolism

decreased platelet serotonin level ( J:7327 )

• much reduced levels of serotonin in platelets and in each large dense granule

abnormal blood coagulation ( J:7327 )

abnormal platelet dense granule physiology ( J:7327 )

• less secretion of dense granule contents and of lysozymal enzymes in comparison to controls (1/2 normal in response to thrombin)

increased bleeding time ( J:7327 )

reproductive system

female infertility ( J:15331 )

♀ • about 1 in 7 females is sterile

vision/eye

decreased eye pigmentation ( J:15331 )

• at birth but normal in adults

hematopoietic system

decreased platelet dense granule number ( J:7327 )

• decreased numbers of dense granules/platelet

• platelet numbers are normal

decreased platelet serotonin level ( J:7327 )

• much reduced levels of serotonin in platelets and in each large dense granule

abnormal platelet dense granule physiology ( J:7327 )

• less secretion of dense granule contents and of lysozymal enzymes in comparison to controls (1/2 normal in response to thrombin)

behavior/neurological

abnormal maternal nurturing ( J:15331 )

♀ • females that survive pregnancy and lactation make poor mothers

integument

abnormal coat/hair pigmentation ( J:6739 , J:15331 )

• about 6% of homozygotes have normal color patches (J:6739)

• if more than 5% of coat is normally pigmented then germinal reversion is also seen (J:6739)

diluted coat color ( J:15331 )

• greatest at the base of hairs but affecting the whole hair

• snout, ears, feet and tail particularly lighter than controls

• the characteristic yellowish mask around the eyes is diluted to near-white

white spotting ( J:15331 )

• white "mask" around eyes

• a long, narrow mid ventral white streak is occasionally observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hermansky-Pudlak syndrome 2		DOID:0060540	OMIM:608233	J:52879 , J:80751
platelet storage pool deficiency		DOID:2223	OMIM:185050	J:7327

Genotype
MGI:3702282

hm3

• Allelic Composition: Ap3b1^pe/Ap3b1^pe
• Genetic Background: involves: C3H/He * C57BL/6J

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:6219 )

• kidney glucuronidase levels elevated 2.5X over controls

• kidney galactosidase and mannosidase levels are also elevated

• increased kidney synthesis of glucuronidase

• decreased secretion of beta-galactosidase but not other lysosome enzymes

reproductive system

thin endometrium ( J:307475 )

♀ • the endometrial stroma and endometrial epithelium of the uterus are thinner than those in controls

short uterine horn ( J:307475 )

♀

thin uterine horn ( J:307475 )

♀

small uterus ( J:307475 )

♀

uterus hypoplasia ( J:307475 )

♀

decreased litter size ( J:307475 )

♀

renal/urinary system

abnormal proximal convoluted tubule morphology ( J:6219 )

• increased hypertrophy of proximal tubule cells after testosterone treatment as compared to controls

Genotype
MGI:5315726

ht4

• Allelic Composition: Ap3b1^pe/Ap3b1^pe-6J
• Genetic Background: (B6.C3-Ap3b1^pe x C3H/HeJ-Ap3b1^pe-6J)F1

integument

diluted coat color ( J:78804 )

pigmentation

diluted coat color ( J:78804 )

hypopigmentation ( J:78804 )

• ears, feet, and tail of mutant mice are lighter than wild-type

Genotype
MGI:5315768

ht5

• Allelic Composition: Ap3b1^pe/Ap3b1^pe-9J
• Genetic Background: (B6.C3-Ap3b1^pe x C57BL/6J-Ap3b1^pe-9J)F1

pigmentation

hypopigmentation ( J:52521 )

• coat, ears, feet, and tail have reduced pigmentation

Genotype
MGI:3586968

cx6

• Allelic Composition: Ap3b1^pe/Ap3b1^pe; Hps1^ep/Hps1^ep
• Genetic Background: involves: C3H/He * C3HeB/FeJ * C57BL/6J

respiratory system

increased lung weight ( J:85431 )

• increased ratio of lung wet weight to body weight

lung inflammation ( J:85431 )

• large numbers of inflammatory cells increasing with age (5.6x normal at 1 year)

• most inflammatory cells in lungs are mononuclear macrophage

abnormal lung epithelium morphology ( J:85431 )

• lung epithelium with large numbers of giant cells containing "foamy" material

abnormal type II pneumocyte morphology ( J:85431 )

• type II cells and lamellar bodies are significantly enlarged

enlarged alveolar lamellar bodies ( J:85431 )

• massive lamellar bodies in type II cells (2.5-4.5 um and rarely to 28 um), engorged with surfactant

abnormal lung interstitium morphology ( J:85431 )

• large open air spaces in the lung parenchyma

emphysema ( J:85431 )

abnormal lung hysteresivity ( J:85431 )

• abnormal respiratory function as determined by in vivo measurement of lung hysteresivity

immune system

abnormal monocyte morphology ( J:85431 )

• mononuclear macrophage are of normal size at 8-15 weeks of age but enlarged at 1 year and containing foamy material

lung inflammation ( J:85431 )

• large numbers of inflammatory cells increasing with age (5.6x normal at 1 year)

• most inflammatory cells in lungs are mononuclear macrophage

hematopoietic system

abnormal monocyte morphology ( J:85431 )

• mononuclear macrophage are of normal size at 8-15 weeks of age but enlarged at 1 year and containing foamy material

growth/size/body

increased lung weight ( J:85431 )

• increased ratio of lung wet weight to body weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hermansky-Pudlak syndrome 1		DOID:0060539	OMIM:203300	J:85431
Hermansky-Pudlak syndrome 2		DOID:0060540	OMIM:608233	J:85431