Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Lorne A Clarke,   University of British Columbia

Description
At birth, mice that are homozygous null for the Idua gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No alpha-L-iduronidase enzyme activity or mRNA is detected. By three weeks of age, homozygous null mice develop a flattened facial profile and a thickening of digits. Defective bone formation is noticeable by fifteen weeks, characterized by a broadening and thickening of long bones. Evidence of lysosomal storage disorder is apparent in cells of the reticuloendothelial system at four weeks. By eight weeks progressive evidence of lysosomal storage is seen in Kupffer cells, splenic sinusoidal lining cells, chondrocytes, glial and Purkinje cells. This animal model is suitable for use in studies investigating the lysosomal storage disorder mucopolysaccharidosis type I (MPS I).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Idua^tm1Clk allele

004083

NOD.129(B6)-Prkdcscid Iduatm1Clk/J

View Strains carrying   Idua^tm1Clk     (1 strain)

Strains carrying other alleles of Idua

017681

B6.129S-Iduatm1.1Kmke/J

View Strains carrying other alleles of Idua     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Hurler Syndrome

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Hurler-Scheie Syndrome   (IDUA) Scheie Syndrome   (IDUA)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Idua^tm1Clk/Idua^tm1Clk

        B6.129-Idua^tm1Clk/J

• mortality/aging
• decreased survivor rate
  • only 21% of males and 40% of females live past 12 months of age   (MGI Ref ID J:130215)
  • the median survival age for males is 32 weeks and for females 48 weeks   (MGI Ref ID J:130215)
  • the rapid loss of male mice starts around 7 months of age and for females at 9 months of age   (MGI Ref ID J:130215)
• growth/size phenotype
• increased body weight
  • body weight of mice becomes significantly greater than controls at 11 weeks of age for females and 14 weeks of age for males   (MGI Ref ID J:130215)
  • mice remain heavier for at 34 weeks of age   (MGI Ref ID J:130215)
• behavior/neurological phenotype
• abnormal learning/memory/conditioning
  • mice have less habituation to an open field as determined by less decrease in locomotor activity on the third exposure compared to the first   (MGI Ref ID J:130215)
• • abnormal long term spatial reference memory
    • 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   (MGI Ref ID J:130215)
  • abnormal spatial learning
    • 4-month old mice take longer than controls to reach a hidden platform in a morris water maze   (MGI Ref ID J:130215)
    • differences were not observed at 2, 6, and 8 months of age   (MGI Ref ID J:130215)
• abnormal response to novel object
  • 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   (MGI Ref ID J:130215)
• decreased startle reflex
  • 61.0% of mutant mice do no react to an acoustic startle compared to 9.7% of control mice that do not react   (MGI Ref ID J:130215)
• hypoactivity
  • mice have decreased horizontal activity when placed into a new environment   (MGI Ref ID J:130215)
• increased anxiety-related response
  • 8 month old males bury fewer marblesthan controls, which is suggestive of increased anxiety   (MGI Ref ID J:130215)
• homeostasis/metabolism phenotype
• increased urine glycosaminoglycan level
  • urinary secretion of glycosaminoglycans is 4- to 20-fold higher than controls regardless of age   (MGI Ref ID J:130215)
• renal/urinary system phenotype
• increased urine glycosaminoglycan level
  • urinary secretion of glycosaminoglycans is 4- to 20-fold higher than controls regardless of age   (MGI Ref ID J:130215)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Idua^tm1Clk/Idua^tm1Clk

        involves: 129S1/Sv * 129X1/SvJ

• mortality/aging
• premature death
  • early deaths beginning around 25 weeks of age   (MGI Ref ID J:47999)
  • average life span around 48 weeks   (MGI Ref ID J:47999)
  • all homozygotes dead by 85 weeks   (MGI Ref ID J:47999)
• growth/size phenotype
• postnatal growth retardation
  • normal growth until about 30 weeks of age after which time growth slows considerably   (MGI Ref ID J:47999)
• craniofacial phenotype
• abnormal cranium morphology
  • broadened cranium   (MGI Ref ID J:47999)
• broad head
  • foreshortened snout   (MGI Ref ID J:47999)
  • protruding nasal bridge   (MGI Ref ID J:47999)
  • widely set eyes   (MGI Ref ID J:47999)
  • broadening of face beginning around 4 weeks of age   (MGI Ref ID J:39522)
• limbs/digits/tail phenotype
• abnormal limb morphology
  • swelling of limbs   (MGI Ref ID J:47999)
• • abnormal autopod morphology
    • broadened   (MGI Ref ID J:39522)
  • • abnormal digit morphology
      • thickened digits   (MGI Ref ID J:39522)
  • abnormal tibia morphology
    • tibial growth plate thickened at 6 weeks of age   (MGI Ref ID J:47999)
    • increased numbers of chondrocytes   (MGI Ref ID J:47999)
• skeleton phenotype
• abnormal axial skeleton morphology   (MGI Ref ID J:47999)
• • abnormal cranium morphology
    • broadened cranium   (MGI Ref ID J:47999)
  • abnormal rib morphology
    • increased thickness   (MGI Ref ID J:39522)
    • flaring of anterior end of ribs and general widening   (MGI Ref ID J:47999)
  • abnormal vertebrae morphology
    • reduced tapering   (MGI Ref ID J:47999)
  • kyphosis
    • thoracic kyphosis apparent at 57 weeks of age   (MGI Ref ID J:47999)
• abnormal chondrocyte morphology
  • lysosomal storage in chondrocytes of articular surfaces and trachea beginning around 4 weeks of age   (MGI Ref ID J:39522)
• abnormal joint morphology
  • hip dislocation in some older mice   (MGI Ref ID J:47999)
• abnormal long bone morphology
  • irregular primary trabeculae   (MGI Ref ID J:47999)
  • retained cartilage with ossified bone   (MGI Ref ID J:47999)
• • abnormal long bone diaphysis morphology
    • thickened diaphyses   (MGI Ref ID J:47999)
  • abnormal long bone hypertrophic chondrocyte zone
    • hypertrophic zone somewhat disorganized   (MGI Ref ID J:47999)
  • abnormal tibia morphology
    • tibial growth plate thickened at 6 weeks of age   (MGI Ref ID J:47999)
    • increased numbers of chondrocytes   (MGI Ref ID J:47999)
• increased osteoblast cell number   (MGI Ref ID J:47999)
• behavior/neurological phenotype
• abnormal gait
  • dragging of hind quarters   (MGI Ref ID J:47999)
• hypoactivity
  • declining mobility with age   (MGI Ref ID J:47999)
• cellular phenotype
• lysosomal protein accumulation
  • abnormal lysosomal storage in all tissues examined particularly the reticuloendothelial system   (MGI Ref ID J:39522)
  • 15-20% of hepatocyte cytoplasm taken up by lysosomes by 8 weeks of age   (MGI Ref ID J:39522)
• nervous system phenotype
• abnormal neuron morphology
  • cytoplasmic vacuolation seen in neurons of the cerebral cortex at 8 weeks of age   (MGI Ref ID J:39522)
  • increased ganglioside levels   (MGI Ref ID J:47999)
• • abnormal Purkinje cell morphology
    • cytoplasmic vacuolation seen at 8 weeks of age   (MGI Ref ID J:39522)
  • • Purkinje cell degeneration
      • progressive loss of Purkinje cells with age   (MGI Ref ID J:47999)
• liver/biliary system phenotype
• pale liver
  • by 8 weeks of age   (MGI Ref ID J:39522)
• homeostasis/metabolism phenotype
• increased urine glycosaminoglycan level
  • 3 fold increase in excretion of glycosaminoglycan   (MGI Ref ID J:39522)
• vision/eye phenotype
• abnormal eye morphology
  • thickened periorbital tissue sometimes causes partial closure of eyes   (MGI Ref ID J:47999)
• cardiovascular system phenotype
• congestive heart failure
  • sometimes observed on autopsy after death   (MGI Ref ID J:47999)
• renal/urinary system phenotype
• increased urine glycosaminoglycan level
  • 3 fold increase in excretion of glycosaminoglycan   (MGI Ref ID J:39522)
• integument phenotype
• disheveled coat
  • tattered appearance   (MGI Ref ID J:47999)
• sparse hair
  • thin coat   (MGI Ref ID J:47999)

Idua^tm1Clk/Idua^tm1Clk

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• homeostasis/metabolism phenotype
• abnormal circulating enzyme level
  • blood levels of a serpin-protease complex containing heparin cofactor II and thrombin (HCII-T) are elevated in mice as they age   (MGI Ref ID J:138341)
  • even at under 10 weeks of age, circulating levels of HCII-T are 3-4 fold higher than controls   (MGI Ref ID J:138341)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Idua^tm1Clk related

Developmental Biology Research
Skeletal Defects

Internal/Organ Research
Heart Abnormalities
Liver Defects
Lymphoid Tissue Defects
Spleen Defects

Metabolism Research

Neurobiology Research
Cerebellar Defects
Metabolic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Iduatm1Clk
Allele Name		targeted mutation 1, Lorne A Clarke
Allele Type		Targeted (knock-out)
Mutation Made By		Lorne Clarke,   University of British Columbia
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Idua, iduronidase, alpha-L-
Chromosome		5
Gene Common Name(s)		IDA; MPS1;
Molecular Note		A neomycin selection cassette was inserted into exon 6. RT-PCR analysis on RNA derived from liver and kidney of homozygous mice demonstrated that no detectable transcript was produced from this allele. Enzymatic activity assays on homogenates of liver,kidney, brain and tail clippings of homozygous mice confirmed that no functional protein was expressed from this allele. [MGI Ref ID J:39522]

Genotyping

Genotyping Information

Genotyping Protocols

Idua^tm1Clk, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Clarke LA; Russell CS; Pownall S; Warrington CL; Borowski A; Dimmick JE ; Toone J ; Jirik FR. 1997. Murine mucopolysaccharidosis type I: targeted disruption of the murine alpha-L-iduronidase gene. Hum Mol Genet 6(4):503-11. [PubMed: 9097952]  [MGI Ref ID J:39522]

Additional References

Idua^tm1Clk related

Garcia-Rivera MF; Colvin-Wanshura LE; Nelson MS; Nan Z; Khan SA; Rogers TB; Maitra I; Low WC; Gupta P. 2007. Characterization of an immunodeficient mouse model of mucopolysaccharidosis type I suitable for preclinical testing of human stem cell and gene therapy. Brain Res Bull 74(6):429-38. [PubMed: 17920451]  [MGI Ref ID J:139626]

Langford-Smith K; Arasaradnam M; Wraith JE; Wynn R; Bigger BW. 2010. Evaluation of heparin cofactor II-thrombin complex as a biomarker on blood spots from mucopolysaccharidosis I, IIIA and IIIB mice. Mol Genet Metab 99(3):269-74. [PubMed: 19926322]  [MGI Ref ID J:158031]

Palpant NJ; Bedada FB; Peacock B; Blazar BR; Metzger JM; Tolar J. 2011. Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies. Am J Physiol Heart Circ Physiol 300(1):H356-65. [PubMed: 21076027]  [MGI Ref ID J:168500]

Pan D; Sciascia A nd; Vorhees CV; Williams MT. 2008. Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome. Brain Res 1188:241-53. [PubMed: 18022143]  [MGI Ref ID J:130215]

Randall DR; Colobong KE; Hemmelgarn H; Sinclair GB; Hetty E; Thomas A; Bodamer OA; Volkmar B; Fernhoff PM; Casey R; Chan AK; Mitchell G; Stockler S; Melancon S; Rupar T; Clarke LA. 2008. Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Mol Genet Metab 94(4):456-61. [PubMed: 18511319]  [MGI Ref ID J:138341]

Randall DR; Sinclair GB; Colobong KE; Hetty E; Clarke LA. 2006. Heparin cofactor II-thrombin complex in MPS I: A biomarker of MPS disease. Mol Genet Metab 88(3):235-43. [PubMed: 16497528]  [MGI Ref ID J:110431]

Russell C; Hendson G; Jevon G; Matlock T; Yu J; Aklujkar M; Ng KY ; Clarke LA. 1998. Murine MPS I: insights into the pathogenesis of Hurler syndrome. Clin Genet 53(5):349-61. [PubMed: 9660052]  [MGI Ref ID J:47999]

Wang D; Zhang W; Kalfa TA; Grabowski G; Davies S; Malik P; Pan D. 2009. Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome. Proc Natl Acad Sci U S A 106(47):19958-63. [PubMed: 19903883]  [MGI Ref ID J:154744]

Wilson S; Hashamiyan S; Clarke L; Saftig P; Mort J; Dejica VM; Bromme D. 2009. Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities. Am J Pathol 175(5):2053-62. [PubMed: 19834056]  [MGI Ref ID J:154691]

Wolf DA; Hanson LR; Aronovich EL; Nan Z; Low WC; Frey WH 2nd; McIvor RS. 2012. Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration. Mol Genet Metab 106(1):131-4. [PubMed: 22420937]  [MGI Ref ID J:183240]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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