Mouse Genome Informatics
hm1
     Ap3b1pe/Ap3b1pe
B6.C3-Ap3b1pe/J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
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 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 alveoli ( 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 serotonin level ( J:7327 )
• less than 3% of normal platelet serotonin levels
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

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 founds
decreased platelet ADP level ( J:7327 )
• platelet ADP levels are much lower than in C57BL/6J controls
decreased platelet ATP level ( J:7327 )
• platelet ATP levels are much lower than in C57BL/6J controls
abnormal 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

cellular
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
 OMIM IDRef(s)
Storage Pool Platelet Disease 185050 J:7327


Mouse Genome Informatics
hm2
     Ap3b1pe/Ap3b1pe
involves: C3H/He
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
partial neonatal lethality ( J:15331 )
• smaller litter sizes at birth
postnatal lethality ( J:15331 )
• reduced litter sizes at weaning
pregnancy-related premature death ( J:15331 )
• females tend to die during pregnancy and while nursing

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 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)

reproductive system
female infertility ( J:15331 )
• about 1 in 7 females is sterile (J:15331)

vision/eye
decreased eye pigmentation ( J:15331 )
• at birth but normal in adults

hematopoietic system
abnormal 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 (J:15331)

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 Genome Informatics
hm3
     Ap3b1pe/Ap3b1pe
involves: C3H/He * C57BL/6J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
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

renal/urinary system
abnormal proximal convoluted tubule morphology ( J:6219 )
• increased hypertrophy of proximal tubule cells after testosterone treatment as compared to controls


Mouse Genome Informatics
ht4
     Ap3b1pe/Ap3b1pe-6J
(B6.C3-Ap3b1pe x C3H/HeJ-Ap3b1pe-6J)F1
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
integument

pigmentation
hypopigmentation ( J:78804 )
• ears, feet, and tail of mutant mice are lighter than wild-type


Mouse Genome Informatics
ht5
     Ap3b1pe/Ap3b1pe-9J
(B6.C3-Ap3b1pe x C57BL/6J-Ap3b1pe-9J)F1
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
pigmentation
hypopigmentation ( J:52521 )
• coat, ears, feet, and tail have reduced pigmentation


Mouse Genome Informatics
cx6
     Ap3b1pe/Ap3b1pe
Hps1ep/Hps1ep
involves: C3H/He * C3HeB/FeJ * C57BL/6J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
respiratory system
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
increased lung weight ( J:85431 )
• increased ratio of lung wet weight to body weight
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