Phenotypes associated with this allele

• Allele Symbol: Ap3d1^mh
• Allele Name: mocha
• Allele ID: MGI:1856083
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ap3d1^mh/Ap3d1^mh	B6.C3-Grxcr1^pi	MGI:3528946
hm2	Ap3d1^mh/Ap3d1^mh	STOCK Mfsd12^gr +/+ Ap3d1^mh/J	MGI:3527905
cx3	Ap3d1^mh Mfsd12^+/Ap3d1^+ Mfsd12^gr	STOCK Mfsd12^gr +/+ Ap3d1^mh/J	MGI:3765903

Genotype
MGI:3528946

hm1

• Allelic Composition: Ap3d1^mh/Ap3d1^mh
• Genetic Background: B6.C3-Grxcr1^pi

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:5511 )

• 50-70% die between birth and 4 weeks of age depending on genetic background

pigmentation

diluted coat color ( J:5511 )

• both yellow (phaeomelanin) and black (eumelanin) hairs are diluted

• hairs in ear and around genitalia are white

decreased eye pigmentation ( J:5511 )

• absence of visible eye pigment at birth

• eyes of adult mice appear deep red

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:5511 )

head tilt ( J:5511 )

• all do not overtly display this but all show imbalance when handled

hyperactivity ( J:5511 )

• contributes to poor breeding and offspring neglect

growth/size/body

postnatal growth retardation ( J:5511 )

• at all ages mice are smaller than normal littermates

hearing/vestibular/ear

abnormal inner ear morphology ( J:5511 )

• in surviving homozygous ranging 27 days or more

organ of Corti degeneration ( J:5511 )

• >by 100 days of age there is extensive loss of hair cells and distortion of supporting cells

abnormal stria vascularis morphology ( J:5511 )

• almost always reduced

abnormal inner ear vestibule morphology ( J:5511 )

abnormal otolith morphology ( J:5511 , J:89392 )

• inconsistent occurrence of variable amounts and distribution of crystals in some mutants (J:5511)

abnormal hearing physiology ( J:5511 )

• mice are initially hypersensitive to sound

• hearing loss progresses to complete deafness between 3-6 months of age

absent linear vestibular evoked potential ( J:89392 )

reproductive system

abnormal fertility/fecundity ( J:5511 )

• hyperactivity contributes to poor breeding performance and offspring neglect

vision/eye

decreased eye pigmentation ( J:5511 )

• absence of visible eye pigment at birth

• eyes of adult mice appear deep red

nervous system

decreased brain zinc level ( J:50662 )

• loss of vesicular zinc in the CNS, most notable in the neocortical and hippocampal regions

cochlear ganglion degeneration ( J:5511 )

• severe loss of cells in the spiral ganglion in animals over 100-days-old

homeostasis/metabolism

increased bleeding time ( J:88018 )

• greater than 15 minutes compared to normal 2 minute bleeding time

decreased brain zinc level ( J:50662 )

• loss of vesicular zinc in the CNS, most notable in the neocortical and hippocampal regions

integument

diluted coat color ( J:5511 )

• both yellow (phaeomelanin) and black (eumelanin) hairs are diluted

• hairs in ear and around genitalia are white

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hermansky-Pudlak syndrome 2		DOID:0060540	OMIM:608233	J:29151
platelet storage pool deficiency		DOID:2223	OMIM:185050	J:29151

Genotype
MGI:3527905

hm2

• Allelic Composition: Ap3d1^mh/Ap3d1^mh
• Genetic Background: STOCK Mfsd12^gr +/+ Ap3d1^mh/J

mortality/aging

postnatal lethality ( J:7485 )

• the percent homozygotes surviving to weaning is between 16% and 23% of Mendelian prediction, with some variation over time

• the percent of newborn homozygotes is between 47% and 97% of Mendelian prediction, with many dying within the first two or three days after birth

nervous system

abnormal nervous system physiology ( J:94942 )

• synaptic zinc levels are reduced throughout the brain

abnormal spike wave discharge ( J:59842 )

• spike discharge episodes of .25-1 mV amplitude and approximately 0.5-2 seconds duration observed for 4 of 5 mocha homozygotes, more frequent than in mocha 2 Jackson homozygotes

abnormal brain wave pattern ( J:96307 )

• electrocorticograms from most awake homozygotes show a constant, high voltage (300-600 microvolts), bilaterally synchronous theta wave pattern that is diminished by chloral-hydrate anesthetization

• in some homozygotes there is unilateral hemispheric predominance of the altered theta frequency

• sleep onset causes generalized slowing of cortical activity with sharp waves similar to normal controls

enhanced sensorimotor gating ( J:59842 )

abnormal synaptic dopamine release ( J:163596 )

• a significant decrease in evoked dopamine release in dorsolateral striatum of

hearing/vestibular/ear

abnormal inner ear vestibule morphology ( J:7485 )

• greatly reduced pigmentation within the vestibular portions of the inner ear, and this is not corrected by supplementing the mother's diet with manganese-zinc

absent otoliths ( J:7485 )

• on a normal diet most mocha homozygotes lack otoconia in both the utricle and saccule of one or both ears, but this developmental defect can be greatly prevented in pups by supplementing the mother's diet with manganese-zinc

abnormal auditory brainstem response ( J:59842 )

• the S1 response, but not the S2 response, is markedly greater than in controls and the auditory gating is significantly enhanced as a result

absent linear vestibular evoked potential ( J:116914 )

• VESPs are absent at the maximum stimulus intensity used

behavior/neurological

abnormal spike wave discharge ( J:59842 )

• spike discharge episodes of .25-1 mV amplitude and approximately 0.5-2 seconds duration observed for 4 of 5 mocha homozygotes, more frequent than in mocha 2 Jackson homozygotes

homeostasis/metabolism

decreased platelet serotonin level ( J:29151 )

• platelet serotonin levels are less than 6% those of normal

decreased platelet aggregation ( J:29151 )

• decreased aggregation both in the presence of high or low concentrations of collagen

increased bleeding time ( J:29151 )

• bleed time is greater than 15 minutes

hematopoietic system

hematopoietic system phenotype ( J:71349 )

N • the invariant chain appears to mature and be degraded with normal kinetics, and to have a normal half-life in LPS stimulated antigen presenting cells,

N • MHC class II transport, peptide binding, and surface expression are normal

abnormal platelet dense granule morphology ( J:29151 )

• although a normal number of dense granules stain with mepacrine, UV flashing is reduced by more than fivefold indicating an abnormal intragranular environment

decreased platelet dense granule number ( J:29151 )

• platelets nearly devoid of dense granules

decreased platelet serotonin level ( J:29151 )

• platelet serotonin levels are less than 6% those of normal

decreased platelet aggregation ( J:29151 )

• decreased aggregation both in the presence of high or low concentrations of collagen

cellular

decreased lysosomal enzyme secretion ( J:29151 )

• lysosomal enzyme levels are increased in kidneys and there is an associated decrease in secretion into the urine

• thrombin-induced secretion of platelet lysosomal enzymes glucuronidase and galactosidase is only 30% to 45% of normal values and is not corrected by the addition of adenosine diphosphate

pigmentation

abnormal retina pigment epithelium morphology ( J:29151 )

• although homozygotes do not have the giant granules that are found in the retinal pigment epithelial cells of beige mice, they do have enlarged retinal pigment granules

vision/eye

abnormal retina pigment epithelium morphology ( J:29151 )

• although homozygotes do not have the giant granules that are found in the retinal pigment epithelial cells of beige mice, they do have enlarged retinal pigment granules

renal/urinary system

abnormal proximal convoluted tubule morphology ( J:29151 )

• higher than normal autofluorescence, typical of ceroid-like pigment, is found in proximal tubules

Genotype
MGI:3765903

cx3

• Allelic Composition: Ap3d1^mh Mfsd12⁺/Ap3d1⁺ Mfsd12^gr
• Genetic Background: STOCK Mfsd12^gr +/+ Ap3d1^mh/J

nervous system

abnormal brain wave pattern ( J:96307 )

• electrocorticograms of mocha heterozygotes show occasional brief bursts of lower voltage theta waves, which are a less pronounced abnormality than in homozygotes