Phenotypes associated with this allele

• Allele Symbol: Idua^tm1Clk
• Allele Name: targeted mutation 1, Lorne A Clarke
• Allele ID: MGI:2176236
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Idua^tm1Clk/Idua^tm1Clk	B6.129-Idua^tm1Clk/J	MGI:3839661
hm2	Idua^tm1Clk/Idua^tm1Clk	involves: 129S1/Sv * 129X1/SvJ	MGI:3587410
hm3	Idua^tm1Clk/Idua^tm1Clk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3839657
cx4	Prkdc^scid/Prkdc^scid Idua^tm1Clk/Idua^+	NOD.Cg-Prkdc^scid Idua^tm1Clk/J	MGI:3580455
cx5	Prkdc^scid/Prkdc^scid Idua^tm1Clk/Idua^tm1Clk	NOD.Cg-Prkdc^scid Idua^tm1Clk/J	MGI:3580456

Genotype
MGI:3839661

hm1

• Allelic Composition: Idua^tm1Clk/Idua^tm1Clk
• Genetic Background: B6.129-Idua^tm1Clk/J

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

mortality/aging

decreased survivor rate ( J:130215 )

• only 21% of males and 40% of females live past 12 months of age

• the median survival age for males is 32 weeks and for females 48 weeks

• the rapid loss of male mice starts around 7 months of age and for females at 9 months of age

growth/size/body

increased body weight ( J:130215 )

• body weight of mice becomes significantly greater than controls at 11 weeks of age for females and 14 weeks of age for males

• mice remain heavier for at 34 weeks of age

behavior/neurological

abnormal learning/memory/conditioning ( J:130215 )

• mice have less habituation to an open field as determined by less decrease in locomotor activity on the third exposure compared to the first

abnormal spatial learning ( J:130215 )

• 4-month old mice take longer than controls to reach a hidden platform in a morris water maze

• differences were not observed at 2, 6, and 8 months of age

abnormal long-term spatial reference memory ( J:130215 )

• mice at 4 or 8 months of age swim further away from target than controls both 1 day and 7 days after last learning session in a morris water maze

increased anxiety-related response ( J:130215 )

• 8 month old males bury fewer marblesthan controls, which is suggestive of increased anxiety

abnormal response to novel object ( J:130215 )

• control mice 8 months of age spent 66% of the time exploring a novel object whereas the mutant mice only spent 54% of the time exploring the novel object

decreased startle reflex ( J:130215 )

• 61.0% of mutant mice do no react to an acoustic startle compared to 9.7% of control mice that do not react

decreased locomotor activity ( J:130215 )

• mice have decreased horizontal activity when placed into a new environment

homeostasis/metabolism

increased urine glycosaminoglycan level ( J:130215 )

• urinary secretion of glycosaminoglycans is 4- to 20-fold higher than controls regardless of age

renal/urinary system

increased urine glycosaminoglycan level ( J:130215 )

• urinary secretion of glycosaminoglycans is 4- to 20-fold higher than controls regardless of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis I		DOID:12802		J:130215

Genotype
MGI:3587410

hm2

• Allelic Composition: Idua^tm1Clk/Idua^tm1Clk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

respiratory system

prominent nasal bridge ( J:47999 )

• protruding nasal bridge

mortality/aging

premature death ( J:47999 )

• early deaths beginning around 25 weeks of age

• average life span around 48 weeks

• all homozygotes dead by 85 weeks

growth/size/body

broad face ( J:39522 )

• broadening of face beginning around 4 weeks of age

prominent nasal bridge ( J:47999 )

• protruding nasal bridge

short snout ( J:47999 )

• foreshortened snout

postnatal growth retardation ( J:47999 )

• normal growth until about 30 weeks of age after which time growth slows considerably

craniofacial

increased cranium width ( J:47999 )

• broadened cranium

broad face ( J:39522 )

• broadening of face beginning around 4 weeks of age

prominent nasal bridge ( J:47999 )

• protruding nasal bridge

short snout ( J:47999 )

• foreshortened snout

limbs/digits/tail

abnormal limb morphology ( J:47999 )

• swelling of limbs

increased autopod size ( J:39522 )

• broadened

abnormal digit morphology ( J:39522 )

• thickened digits

hip dislocation ( J:47999 )

• hip dislocation in some older mice

abnormal tibia morphology ( J:47999 )

• tibial growth plate thickened at 6 weeks of age

• increased numbers of chondrocytes

skeleton

hip dislocation ( J:47999 )

• hip dislocation in some older mice

abnormal long bone morphology ( J:47999 )

• irregular primary trabeculae

• retained cartilage with ossified bone

abnormal tibia morphology ( J:47999 )

• tibial growth plate thickened at 6 weeks of age

• increased numbers of chondrocytes

abnormal long bone diaphysis morphology ( J:47999 )

• thickened diaphyses

abnormal long bone hypertrophic chondrocyte zone ( J:47999 )

• hypertrophic zone somewhat disorganized

abnormal axial skeleton morphology ( J:47999 )

increased cranium width ( J:47999 )

• broadened cranium

abnormal rib morphology ( J:39522 , J:47999 )

• increased thickness (J:39522)

• flaring of anterior end of ribs and general widening (J:47999)

kyphosis ( J:47999 )

• thoracic kyphosis apparent at 57 weeks of age

abnormal vertebrae morphology ( J:47999 )

• reduced tapering

increased osteoblast cell number ( J:47999 )

abnormal chondrocyte morphology ( J:39522 )

• lysosomal storage in chondrocytes of articular surfaces and trachea beginning around 4 weeks of age

behavior/neurological

abnormal gait ( J:47999 )

• dragging of hind quarters

decreased locomotor activity ( J:47999 )

• declining mobility with age

cellular

lysosomal protein accumulation ( J:39522 )

• abnormal lysosomal storage in all tissues examined particularly the reticuloendothelial system

• 15-20% of hepatocyte cytoplasm taken up by lysosomes by 8 weeks of age

nervous system

abnormal neuron morphology ( J:39522 , J:47999 )

• cytoplasmic vacuolation seen in neurons of the cerebral cortex at 8 weeks of age (J:39522)

• increased ganglioside levels (J:47999)

abnormal Purkinje cell morphology ( J:39522 )

• cytoplasmic vacuolation seen at 8 weeks of age

Purkinje cell degeneration ( J:47999 )

• progressive loss of Purkinje cells with age

liver/biliary system

pale liver ( J:39522 )

• by 8 weeks of age

homeostasis/metabolism

increased urine glycosaminoglycan level ( J:39522 )

• 3 fold increase in excretion of glycosaminoglycan

vision/eye

abnormal eye morphology ( J:47999 )

• thickened periorbital tissue sometimes causes partial closure of eyes

ocular hypertelorism ( J:47999 )

• widely set eyes

cardiovascular system

congestive heart failure ( J:47999 )

• sometimes observed on autopsy after death

renal/urinary system

increased urine glycosaminoglycan level ( J:39522 )

• 3 fold increase in excretion of glycosaminoglycan

integument

sparse hair ( J:47999 )

• thin coat

disheveled coat ( J:47999 )

• tattered appearance

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis I		DOID:12802		J:39522 , J:47999

Genotype
MGI:3839657

hm3

• Allelic Composition: Idua^tm1Clk/Idua^tm1Clk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism

abnormal circulating enzyme level ( J:138341 )

• blood levels of a serpin-protease complex containing heparin cofactor II and thrombin (HCII-T) are elevated in mice as they age

• even at under 10 weeks of age, circulating levels of HCII-T are 3-4 fold higher than controls

Genotype
MGI:3580455

cx4

• Allelic Composition: Prkdc^scid/Prkdc^scid; Idua^tm1Clk/Idua⁺
• Genetic Background: NOD.Cg-Prkdc^scid Idua^tm1Clk/J

craniofacial

short snout ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

broad head ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

small ears ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

hearing/vestibular/ear

small ears ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

vision/eye

enophthalmos ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

integument

rough coat ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

growth/size/body

short snout ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

broad head ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

small ears ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

Genotype
MGI:3580456

cx5

• Allelic Composition: Prkdc^scid/Prkdc^scid; Idua^tm1Clk/Idua^tm1Clk
• Genetic Background: NOD.Cg-Prkdc^scid Idua^tm1Clk/J

reproductive system

female infertility ( J:139626 )

♀ • matings between homozygote females and heterozygote males are unsuccessful

behavior/neurological

abnormal motor learning ( J:139626 )

• mice trained on a rotating rod have decreased times of latency in subsequent tests compared to controls

• males have more deficient motor learning than females

• for females, there was some improvement in times of latency at all speeds though never to the degree seen for controls

• training failed to improve time of latency for males at the highest speed tested

impaired coordination ( J:139626 )

• mice have decreased times of latency in rotarod tests

• males have worse impairment than females

pup cannibalization ( J:139626 )

♀ • mothers often cannibalize their offspring

craniofacial

abnormal zygomatic bone morphology ( J:139626 )

• mice have thickening of the zygomatic bone

short snout ( J:139626 )

• mice have a short snout that is more evident in females

broad head ( J:139626 )

• mice have broad head that is more evident in females

small ears ( J:139626 )

• mice have small ears that is more evident in females

hearing/vestibular/ear

small ears ( J:139626 )

• mice have small ears that is more evident in females

homeostasis/metabolism

abnormal homeostasis ( J:139626 )

• tissue levels of glycosaminoglycans are extremely high throughout tissues with highest levels in the liver followed by kidney, lung, spleen, heart and brain

increased urine glycosaminoglycan level ( J:139626 )

• urinary excretion of glycosaminoglycans is 6.5-fold higher than in controls

nervous system

abnormal brain morphology ( J:139626 )

• ganglioside accumulations are observed

abnormal brainstem morphology ( J:139626 )

• high ganglioside accumulations are observed

abnormal striatum morphology ( J:139626 )

• high ganglioside accumulations are observed

abnormal hippocampus morphology ( J:139626 )

• ganglioside accumulations are observed

abnormal cerebellum morphology ( J:139626 )

• ganglioside accumulations are observed

abnormal cerebellar cortex morphology ( J:139626 )

• ganglioside accumulations are observed

renal/urinary system

increased urine glycosaminoglycan level ( J:139626 )

• urinary excretion of glycosaminoglycans is 6.5-fold higher than in controls

skeleton

abnormal zygomatic bone morphology ( J:139626 )

• mice have thickening of the zygomatic bone

vision/eye

enophthalmos ( J:139626 )

• mice have a short snout that is more evident in females

integument

rough coat ( J:139626 )

• mice have a rough coat

growth/size/body

short snout ( J:139626 )

• mice have a short snout that is more evident in females

broad head ( J:139626 )

• mice have broad head that is more evident in females

small ears ( J:139626 )

• mice have small ears that is more evident in females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis I		DOID:12802		J:139626