Phenotypes Associated with This Genotype

Genotype
MGI:5797380

• Allelic Composition: Arsk^{tm1b(KOMP)Wtsi}/Arsk^{tm1b(KOMP)Wtsi}
• Genetic Background: B6N(Cg)-Arsk^{tm1b(KOMP)Wtsi}/J
• Cell Lines: EPD0670_4_A08

Data Sources

IMPC Data for Arsk

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

behavior/neurological

abnormal spatial reference memory ( J:302659 )

• during the first probe trial of a Morris water maze test, mice fail to show target quadrant exploration above the coincidence level, make less target area entries and spend less time in the target area than wild-type controls, suggesting impaired spatial reference memory; however, no differences are observed during the second probe trial

abnormal social/conspecific interaction behavior ( J:302659 )

• in the Sociability and Preference for Social Novelty test (SPSN), 12-month-old mice exhibit time-dependent changes regarding overall proximity as well as approach behavior towards a caged conspecific in comparison with an empty cage, suggesting delayed and altered sociability

cellular

abnormal lysosome physiology ( J:302659 )

• after tyloxapol treatment, isolated liver lysosomes show a 2.5-fold increase in heparan sulfate (HS)

• purified liver lysosomes show increased levels of 2-O-sulfated HS; in contrast, chondroitin sulfate (CS) does not exhibit elevated 2-O-sulfation values

• isolated liver lysosomes show a 10-fold increase in G2S0-containing disaccharides

homeostasis/metabolism

abnormal glycosaminoglycan level ( J:302659 )

• at 12 months of age, mice accumulate significant amounts of total heparan sulfate (HS) in brain, kidney and spleen, with the highest total HS amount found in kidney (5x)

• HS exhibits glucuronate-2-O-sulfated non-reducing ends (NREs) particularly in brain and kidney; recombinant ARSK/GDS efficiently degrades the glucuronate-2-O-sulfated NREs of accumulated HS

• although total chondroitin sulfate (CS) is elevated in the kidney (5x), liver homogenates and purified liver lysosomes exhibit normal CS levels

• no storage pathology/vacuolation is observed in the kidney, liver, lung, trachea, retina or brain

abnormal enzyme/coenzyme activity ( J:302659 )

• a novel specific enzyme assay based on HPLC/MS analysis of 2-aminoacridone-labeled disaccharides showed that the liver is totally devoid of glucuronate-2-sulfatase (GDS) activity, confirming complete loss of glucuronate desulfation

nervous system

nervous system phenotype ( J:302659 )

N • at 12 months of age, mice exhibit no major pathohistological changes in the CNS

renal/urinary system

abnormal kidney inner medulla morphology ( J:302659 )

• at 12 months of age, kidneys exhibit electron-dense bodies in intermediate tubules of the inner medulla, not present in wild-type controls

abnormal kidney outer medulla inner stripe morphology ( J:302659 )

• at 12 months of age, kidneys exhibit electron-dense bodies in the thick ascending limbs of the inner stripe of the outer medulla, not present in wild-type controls; in electron microscopy, the equivalent of these dense bodies appear as lipofuscin-related material

skeleton

decreased bone mineral density ( J:302659 )

• at 24 weeks of age, mice show a moderate reduction in bone mineral density

• however, bone remodeling is relatively normal, and no obvious skeletal phenotype is observed

vision/eye

abnormal retina morphology ( J:211773 )

IMPC - JAX

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis		DOID:12798	OMIM:PS607014	J:302659