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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 | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying Iduatm1Clk allele
004083 NOD.129(B6)-Prkdcscid Iduatm1Clk/J View Strains carrying Iduatm1Clk (1 strain)
Congenic Nomenclature
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.
Iduatm1Clk/Iduatm1Clk
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:Iduatm1Clk 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
| 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 Protocols
Iduatm1Clk, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Iduatm1Clk relatedGarcia-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]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| 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. | ||
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