Phenotypes associated with this allele

• Allele Symbol: Ids^tm1Dkji
• Allele Name: targeted mutation 1, Dong-Kyu Jin
• Allele ID: MGI:6474226
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ot1	Ids^tm1Dkji/Y	involves: 129 * C57BL/6	MGI:6476699
ot2	Ids^tm1Dkji/Y	involves: C57BL/6	MGI:6474227

Genotype
MGI:6476699

ot1

• Allelic Composition: Ids^tm1Dkji/Y
• Genetic Background: involves: 129 * C57BL/6

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

cellular

abnormal lysosome physiology ( J:294523 )

♂ • lysosomal vacuolization is apparent in the stria vascularis and basilar membrane

♂ • however, lysosomal vacuoles are not seen in the stria vascularis

hearing/vestibular/ear

abnormal Reissner membrane morphology ( J:294523 )

♂ • plumping of cells is seen in the Reissner membrane

♂ • cytoplasm vacuolation of both endothelial and mesothelial cells of Reissner membrane

abnormal basilar membrane morphology ( J:294523 )

♂ • lysosomal vacuolization is apparent in the basilar membrane

abnormal spiral ligament morphology ( J:294523 )

♂ • lysosomal vacuolization is apparent in the spiral ligament

middle ear effusion ( J:294523 )

♂ • soft tissue density occupies more space in the middle ear indicating middle ear effusion

♂ • enzyme-replacement therapy reduces the soft tissue density in the middle ear

abnormal tympanic membrane morphology ( J:294523 )

♂ • thickening of the tympanic membrane is seen at 17, but not 7, weeks of age

increased or absent threshold for auditory brainstem response ( J:294523 )

♂ • hearing thresholds for click sounds and tone bursts of 8, 16, and 32 kHz are higher than in wild-type mice at 17 weeks of age

♂ • however, mice exhibit good hearing at 7 weeks of age

♂ • enzyme-replacement treatment for 5 and 10 weeks returns hearing thresholds to similar levels as in wild-type mice

homeostasis/metabolism

middle ear effusion ( J:294523 )

♂ • soft tissue density occupies more space in the middle ear indicating middle ear effusion

♂ • enzyme-replacement therapy reduces the soft tissue density in the middle ear

abnormal glycosaminoglycan level ( J:294523 )

♂ • mice show a 5-fold increase in glycosaminoglycan (GAG) levels in ear tissue at 17 weeks of age

♂ • GAG content is elevated in the cartilaginous matrix of the osseous labyrinth

♂ • enzyme-replacement therapy results in a slight decrease in GAG level in ear tissue

nervous system

abnormal cochlear ganglion morphology ( J:294523 )

♂ • reduction in the number of ganglion cells is seen and the remaining ganglion cells exhibit pale cytoplasm

♂ • parenchymal loss of the spiral ganglion

skeleton

abnormal spiral ligament morphology ( J:294523 )

♂ • lysosomal vacuolization is apparent in the spiral ligament

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis II		DOID:12799	OMIM:309900	J:294523

Genotype
MGI:6474227

ot2

• Allelic Composition: Ids^tm1Dkji/Y
• Genetic Background: involves: C57BL/6

mortality/aging

premature death ( J:294717 )

♂ • most mice die before 1 year of age

growth/size/body

abnormal facial morphology ( J:294717 )

♂ • external facial appearance is different from wild-type mice at 5-6 weeks of age

coarse facial features ( J:294717 )

♂ • coarse facial features are seen at 5-6 weeks of age

large face ( J:294717 )

♂ • face is relatively larger than in wild-type mice

abnormal snout morphology ( J:294717 )

♂ • the snout is more prominent

abnormal body weight ( J:294717 )

♂ • mice are heavier from 4 to 11 weeks of age but after 12 weeks of age, wild-type mice become heavier

behavior/neurological

decreased locomotor activity ( J:294717 )

♂ • physical activity declines around 25 to 30 weeks of age

craniofacial

abnormal facial morphology ( J:294717 )

♂ • external facial appearance is different from wild-type mice at 5-6 weeks of age

coarse facial features ( J:294717 )

♂ • coarse facial features are seen at 5-6 weeks of age

large face ( J:294717 )

♂ • face is relatively larger than in wild-type mice

abnormal snout morphology ( J:294717 )

♂ • the snout is more prominent

homeostasis/metabolism

abnormal glycosaminoglycan level ( J:294717 )

♂ • elevated CAG content is seen in a variety of tissues including the liver, lung, heart, brain, spleen, kidney and skin

♂ • mice treated with a pseudotyped, recombinant adeno-associated virus vector encoding the human IDS gene show clearance of accumulated lysosomal GAG

increased urine glycosaminoglycan level ( J:294717 )

♂ • urinary GAG excretion is greater beginning at 4 weeks of age and is most prominent at 16 and 38 weeks of age

integument

alopecia ( J:294717 )

♂ • sporadic alopecia is seen at 5-6 weeks of age

limbs/digits/tail

abnormal hand joint morphology ( J:294717 )

♂ • the articulation of the foot is restricted in the forelimb and resembles a clawed hand

abnormal hindlimb joint morphology ( J:294717 )

♂ • mice show limitations of the hind limb joint when the tail is pulled back at 7-8 weeks of age

renal/urinary system

increased urine glycosaminoglycan level ( J:294717 )

♂ • urinary GAG excretion is greater beginning at 4 weeks of age and is most prominent at 16 and 38 weeks of age

skeleton

abnormal hand joint morphology ( J:294717 )

♂ • the articulation of the foot is restricted in the forelimb and resembles a clawed hand

abnormal hindlimb joint morphology ( J:294717 )

♂ • mice show limitations of the hind limb joint when the tail is pulled back at 7-8 weeks of age

cellular

abnormal foam cell morphology ( J:294717 )

♂ • many foamy cells are seen in the liver, kidney, lung, heart, brain and lymph node extracts, indicating lysosomal storage

abnormal lysosome physiology ( J:294717 )

♂ • lysosomal accumulation of glycosaminoglycans (GAG)

♂ • many foamy cells are seen in the liver, kidney, lung, heart, brain and lymph node extracts, indicating lysosomal storage

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis II		DOID:12799	OMIM:309900	J:294717