Phenotypes Associated with This Genotype

Genotype
MGI:8329983

• Allelic Composition: Hgsnat^em1Scher/Hgsnat^em1Scher
• Genetic Background: C57BL/6J-Hgsnat^em1Scher

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

behavior/neurological

abnormal gait ( J:381685 )

• mice show an inability to properly couple the movement of the right front paw with the left hind paw and defects in support diagonal, run average speed, duration, and run duration on the CatWalk testing apparatus

• wild-type HSPC transplantation into lethally irradiated homozygotes at 2 months of age improves the gait and locomotor function impairments

short stride length ( J:381685 )

increased locomotor activity ( J:381685 )

• 10-month-old mice show increased mean speed and distance in the open field

• however, time spend in the center, thigmotaxis, and freezing time show no differences

cellular

increased microglial cell activation ( J:381685 )

• microglial activation is seen the brain, kidney, and liver

growth/size/body

enlarged urinary bladder ( J:381685 )

• mice exhibit enlarged bladder

• bladder size is reduced following transplantation with wild-type HPSCs

enlarged liver ( J:381685 )

• hepatomegaly

• transplantation with wild-type HPSCs does not improve hepatomegaly

enlarged spleen ( J:381685 )

• increase in spleen mass indicating splenomegaly

• spleen mass is decreased following transplantation with wild-type HPSCs

hematopoietic system

increased microglial cell activation ( J:381685 )

• microglial activation is seen the brain, kidney, and liver

enlarged spleen ( J:381685 )

• increase in spleen mass indicating splenomegaly

• spleen mass is decreased following transplantation with wild-type HPSCs

homeostasis/metabolism

abnormal glycosaminoglycan level ( J:381685 )

• mice show accumulation of total heparan sulfate within the brain and kidney and the presence of MPS IIC disease-specific non-reducing end carbohydrates in the liver and brain

• single systemic wild-type hematopoietic stem and progenitor cell (HSPC) transplantation into lethally irradiated homozygotes at 2 months of age decreases the MPS IIC disease-specific non-reducing end carbohydrates

immune system

increased microglial cell activation ( J:381685 )

• microglial activation is seen the brain, kidney, and liver

enlarged spleen ( J:381685 )

• increase in spleen mass indicating splenomegaly

• spleen mass is decreased following transplantation with wild-type HPSCs

brain inflammation ( J:381685 )

• CD68 expression is increased in the brain indicating macrophage/microglia activation and phagocytic activity

• CD68 expression is reduced following transplantation with wild-type HPSCs

liver inflammation ( J:381685 )

• an increase of CD68+ cells is seen in the liver suggesting an increase of liver inflammation

• CD68+ cells in the liver are reduced following transplantation with wild-type HPSCs

kidney inflammation ( J:381685 )

• an increase of CD68+ cells is seen in the kidney suggesting an increase of kidney inflammation

• CD68+ cells in the kidney are reduced following transplantation with wild-type HPSCs

liver/biliary system

enlarged liver ( J:381685 )

• hepatomegaly

• transplantation with wild-type HPSCs does not improve hepatomegaly

liver inflammation ( J:381685 )

• an increase of CD68+ cells is seen in the liver suggesting an increase of liver inflammation

• CD68+ cells in the liver are reduced following transplantation with wild-type HPSCs

nervous system

increased microglial cell activation ( J:381685 )

• microglial activation is seen the brain, kidney, and liver

brain inflammation ( J:381685 )

• CD68 expression is increased in the brain indicating macrophage/microglia activation and phagocytic activity

• CD68 expression is reduced following transplantation with wild-type HPSCs

abnormal neuron morphology ( J:381685 )

• increase in neurofilament light chain (NfL) serum levels indicating neuronal damage

• NfL serum levels are decreased following transplantation with wild-type HPSCs

renal/urinary system

enlarged urinary bladder ( J:381685 )

• mice exhibit enlarged bladder

• bladder size is reduced following transplantation with wild-type HPSCs

kidney inflammation ( J:381685 )

• an increase of CD68+ cells is seen in the kidney suggesting an increase of kidney inflammation

• CD68+ cells in the kidney are reduced following transplantation with wild-type HPSCs

abnormal renal glomerulus morphology ( J:381685 )

• kidney shows glomerular hyaline bodies with focal fibrosis and sclerosis

• the number of damaged glomeruli is reduced following transplantation with wild-type HPSCs

glomerulosclerosis ( J:381685 )

• kidney shows sclerosis

renal glomerulus fibrosis ( J:381685 )

• kidney shows focal fibrosis

dilated renal tubule ( J:381685 )

• kidney shows some dilated tubules and vascular spaces

abnormal urination ( J:381685 )

• urine retention

• urine volume is reduced following transplantation with wild-type HPSCs

mortality/aging

mortality/aging ( J:381685 )

N • normal number of homozygotes are obtained and no difference in life span is seen up to 15 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis type IIIC		DOID:0111393	OMIM:252930	J:381685