Phenotypes Associated with This Genotype

Genotype
MGI:3603566

• Allelic Composition: Man2b1^tm1Psa/Man2b1^tm1Psa
• Genetic Background: involves: 129 * C57BL/6J

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

cellular

abnormal lysosome morphology ( J:56659 , J:99812 )

• accumulation of translucent vacuoles are seen in the liver, pancreas, spleen, kidney, eye, thyroid gland, smooth muscle cells, bone, and nervous system (J:56659)

• the cytoplasmic vacuoles are membrane limited and appear either empty or contain some fine granular material (J:56659)

homeostasis/metabolism

abnormal homeostasis ( J:56659 )

• increased levels of neutral oligosaccharides are found in homogenates from the kidney, spleen, brain, and testis

abnormal urine homeostasis ( J:56659 )

• the urine contains high levels of mannose-containing oligosaccharides

nervous system

abnormal brainstem morphology ( J:56659 , J:99812 )

• some vacuolated neurons are seen in several nuclei including the substantia nigra, inferior olive, ambiguus nucleus, cuneate and gracile nuclei, and nuclei in the formatio reticularis (J:99812)

abnormal forebrain morphology ( J:99812 )

abnormal globus pallidus morphology ( J:99812 )

• the lateral globus pallidus contains several vacuolated neurons

abnormal hippocampus morphology ( J:99812 )

abnormal hippocampus CA2 region morphology ( J:99812 )

• vacuolation is most evenly distributed in the neuronal perikarya of the CA2 and CA3 regions while the CA1 and dentate gyrus are weakly or not at all affected

abnormal hippocampus CA3 region morphology ( J:99812 )

• vacuolation is most evenly distributed in the neuronal perikarya of the CA2 and CA3 regions while the CA1 and dentate gyrus are weakly or not at all affected

abnormal cerebral cortex morphology ( J:56659 , J:99812 )

• vacuoles are seen in the isocortex, most prominently in neurons of layers II/III and V/VI (J:56659)

• neurons in the neocortex are variably vacuolated and moderate vacuolation is seen by EM in Purkinje cells and some granular cells (J:99812)

abnormal glial cell morphology ( J:99812 )

• vacuoles are seen in the astrodendroglia and oligodendroglia but not as frequently as in the neurons

abnormal neuron morphology ( J:56659 , J:99812 )

• in the brain vacuoles are most prominent in neurons (J:56659)

abnormal axon morphology ( J:56659 , J:99812 )

• axonal swellings are seen in the central white matter, and pre-terminal portions of the sensory trigeminal and vestibular nerve fibers with the axoplasm containing an accumulation of polymorphous material (J:56659)

abnormal retina photoreceptor morphology ( J:56659 )

• lysosomal storage is seen in the retinal photoreceptors

abnormal cranial ganglia morphology ( J:99812 )

abnormal cochlear ganglion morphology ( J:99812 )

• less severe neuronal vacuolation is seen compared to the trigeminal ganglion

abnormal trigeminal ganglion morphology ( J:99812 )

• marked vacuolation is seen in neurons in the trigeminal ganglion

abnormal vestibular ganglion morphology ( J:99812 )

• less severe neuronal vacuolation is seen compared to the trigeminal ganglion

enhanced long-term potentiation ( J:99812 )

• hippocampal slices from the CA1 region take longer to return to baseline after induction with a single high frequency stimulation and have a higher initial LTP magnitude in response to a second tetanization 2 hours after the initial stimulation

behavior/neurological

abnormal passive avoidance behavior ( J:99812 )

• step-through latency is slightly but significantly decreased

abnormal olfactory discrimination memory ( J:99812 )

• time to obtain reward during training to dig for a food reward in sand is consistently longer in homozygotes at 3 and 12 months of age and slower acquisition is seen during discrimination conditioning following training at 3 but not at 12 months of age

decreased exploration in new environment ( J:99812 )

• a slight but consistent decrease in exploratory activity is seen in open field and dark box tests

abnormal spatial learning ( J:99812 )

• at 3 months but not 12 months of age, during acquisition sessions in a water maze test time to reach the platform is increased, in the first probe trial homozygotes tend to remain in the start quadrant, and in later probe trial 3 month old homozygotes fail to show a preference for the target quadrant unlike wild-type mice

• 12 month old homozygotes spend less time in the target quadrant but do show a preference for the target quadrant

hematopoietic system

abnormal Kupffer cell morphology ( J:56659 )

• accumulation of clear vacuoles is seen in Kupffer cells

abnormal spleen red pulp morphology ( J:56659 )

• lysosomal storage is seen in the sinus endothelia, reticulum cells, macrophages, and trabecular fibroblasts of the red pulp

vision/eye

abnormal eye morphology ( J:56659 )

• lysosomal storage is seen in the ciliary epithelium

abnormal eye muscle morphology ( J:56659 )

• lysosomal storage is seen in the smooth muscle

abnormal retina photoreceptor morphology ( J:56659 )

• lysosomal storage is seen in the retinal photoreceptors

abnormal cornea endothelium morphology ( J:56659 )

• lysosomal storage is seen in the corneal endothelium

abnormal cornea stroma morphology ( J:56659 )

• lysosomal storage is seen in the corneal stroma cells

liver/biliary system

abnormal liver morphology ( J:56659 )

• accumulation of clear vacuoles is seen in sinus endothelial cells

abnormal Kupffer cell morphology ( J:56659 )

• accumulation of clear vacuoles is seen in Kupffer cells

abnormal hepatocyte morphology ( J:56659 )

• accumulation of clear vacuoles is seen in hepatocytes

endocrine/exocrine glands

abnormal pancreatic acinar cell morphology ( J:56659 )

• prominent vacuolization is seen in the acinar cells

skeleton

abnormal skeleton morphology ( J:56659 )

• gross bone architecture is normal but lysosomal storage is seen in osteocytes and endosteal cells of many bones

abnormal spiral ligament fibrocyte morphology ( J:99812 )

• moderate vacuolation in the fibrocytes of the spiral ligament

hearing/vestibular/ear

abnormal cochlea morphology ( J:99812 )

• moderate vacuolation is seen in the fibrocytes of the spiral ligament and the nonspecialized flat epithelium lining the endolymphatic spaces of the cochlea and vestibular apparatus

• however, the organ of Corti and vestibular organ appear normal and brainstem auditory evoked potentials are normal

abnormal spiral ligament fibrocyte morphology ( J:99812 )

• moderate vacuolation in the fibrocytes of the spiral ligament

renal/urinary system

abnormal urine homeostasis ( J:56659 )

• the urine contains high levels of mannose-containing oligosaccharides

abnormal renal tubule epithelium morphology ( J:56659 )

• clear vacuoles are seen in the epithelial cells of the proximal and distal tubules

growth/size/body

decreased body weight ( J:99812 )

• body weight is slightly reduced at 2-3 months of age but is similar to wild-type at 4-5 and 11-12 months of age

immune system

abnormal Kupffer cell morphology ( J:56659 )

• accumulation of clear vacuoles is seen in Kupffer cells

abnormal spleen red pulp morphology ( J:56659 )

• lysosomal storage is seen in the sinus endothelia, reticulum cells, macrophages, and trabecular fibroblasts of the red pulp

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:56659 )

• prominent vacuolization is seen in the acinar cells

muscle

abnormal eye muscle morphology ( J:56659 )

• lysosomal storage is seen in the smooth muscle

cardiovascular system

abnormal Kupffer cell morphology ( J:56659 )

• accumulation of clear vacuoles is seen in Kupffer cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
alpha-mannosidosis		DOID:3413	OMIM:248500	J:56659 , J:99812