Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Lorne 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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Hurler Syndrome - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

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

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

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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

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