Phenotypes Associated with This Genotype

Genotype
MGI:5430642

• Allelic Composition: Arsg^tm1Tdi/Arsg^tm1Tdi
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

Lysosomal storage and cellular alterations in the CNS of Arsg^tm1Tdi/Arsg^tm1Tdi mice

homeostasis/metabolism

abnormal glycosaminoglycan level ( J:185592 )

• strong accumulation of heparan sulfate in the kidney, liver, and brain

vision/eye

short photoreceptor outer segment ( J:254592 )

• progressive with age; no differences are seen at one month of age compared to controls, but the length of the outer segments of rods and cones were shorter in mutant mice at 24 months of age

retina photoreceptor degeneration ( J:254592 )

• the number of photoreceptor cells decreases significantly with increasing age of the animals

thin retina outer nuclear layer ( J:254592 )

• progressive with age; no difference from controls is seen at one month of age, but decreasing thickness is seen at 6, 12 and 24 months of age

decreased total retina thickness ( J:254592 )

• at 6 months of age, mutants retina thickness is significantly decreased at all retinal positions compared to 1 month of KO mice; mutant retinas show more seere thinning at 24 months of age

• retina thickness is further decreased in 24-month-old mutants compared to 6 month old mutant mice

• thickness of the inner retina issimilar in mutant and wild-type mice at all ages analyzed

cellular

lysosomal protein accumulation ( J:185592 )

• lysosomal inclusions and lysosomal storage abnormalities in the nervous system and peripheral tissues including the liver and kidneys

nervous system

abnormal microglial cell morphology ( J:185592 )

• several microglial populations display obvious vacuoles

microgliosis ( J:185592 , J:254592 )

• accompanies neuronal cell death in the cerebellar cortex (J:185592)

• reactive miccrogliosis in outer retina (J:254592)

astrocytosis ( J:185592 , J:254592 )

• accompanies neuronal cell death in the cerebellar cortex (J:185592)

• retinal reactive astrogliosis (J:254592)

• in the outer retina of older mutant mice, the number of activated microglia increases significantly with increasing age of the mutants (J:254592)

abnormal neuron morphology ( J:185592 )

• several neuronal populations display obvious vacuoles

abnormal thalamus neuron morphology ( J:185592 )

• sporadic lysosomal inclusions

abnormal hippocampus neuron morphology ( J:185592 )

• sporadic lysosomal inclusions

abnormal Purkinje cell morphology ( J:185592 )

• prominent lysosomal storage pathology in Purkinje cells of the cerebellum

• storage material shows lamellar to finely granular structures

decreased Purkinje cell number ( J:185592 )

• considerable loss of Purkinje cells becoming evident in mice over 10 months of age

short photoreceptor outer segment ( J:254592 )

• progressive with age; no differences are seen at one month of age compared to controls, but the length of the outer segments of rods and cones were shorter in mutant mice at 24 months of age

retina photoreceptor degeneration ( J:254592 )

• the number of photoreceptor cells decreases significantly with increasing age of the animals

immune system

abnormal macrophage morphology ( J:185592 )

• prominent lysosomal storage pathology in perivascular and meningeal macrophages

abnormal perivascular macrophage morphology ( J:185592 )

• prominent lysosomal storage pathology

abnormal microglial cell morphology ( J:185592 )

• several microglial populations display obvious vacuoles

microgliosis ( J:185592 , J:254592 )

• accompanies neuronal cell death in the cerebellar cortex (J:185592)

• reactive miccrogliosis in outer retina (J:254592)

liver/biliary system

abnormal liver sinusoidal endothelial cell morphology ( J:185592 )

• obvious lysosomal storage pathology is seen in sinusoidal endothelial cells

• accumulation of membrane-limited vacuoles filled with variable amounts of moderately or highly electron-dense and partially water-soluble material

abnormal hepatocyte morphology ( J:185592 )

• obvious lysosomal storage pathology is seen

• accumulation of membrane-limited vacuoles filled with variable amounts of moderately or highly electron-dense and partially water-soluble material

behavior/neurological

abnormal learning/memory/conditioning ( J:185592 )

• age dependent cognitive impairment

impaired passive avoidance behavior ( J:185592 )

• significantly lower step-through latencies in the testing phase at 12 months of age

decreased exploration in new environment ( J:185592 )

• travel less distance in the center of an open field and spend less time in the center

• however, total path length and center entries is similar to wild-type controls

abnormal spatial learning ( J:185592 )

• spend less time in the target quadrant during the probe trial of the water-maze task at 12 months of age but are still able to master the task

renal/urinary system

abnormal kidney morphology ( J:185592 )

• obvious lysosomal storage pathology is seen

abnormal kidney epithelium morphology ( J:185592 )

• the epithelia of the thick ascending limb of Henle's loop and the collecting ducts showed prominent lysosomal storage

cardiovascular system

abnormal liver sinusoidal endothelial cell morphology ( J:185592 )

• obvious lysosomal storage pathology is seen in sinusoidal endothelial cells

• accumulation of membrane-limited vacuoles filled with variable amounts of moderately or highly electron-dense and partially water-soluble material

abnormal perivascular macrophage morphology ( J:185592 )

• prominent lysosomal storage pathology

hematopoietic system

abnormal macrophage morphology ( J:185592 )

• prominent lysosomal storage pathology in perivascular and meningeal macrophages

abnormal perivascular macrophage morphology ( J:185592 )

• prominent lysosomal storage pathology

abnormal microglial cell morphology ( J:185592 )

• several microglial populations display obvious vacuoles

microgliosis ( J:185592 , J:254592 )

• accompanies neuronal cell death in the cerebellar cortex (J:185592)

• reactive miccrogliosis in outer retina (J:254592)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis		DOID:12798	OMIM:PS607014	J:185592