These Idua knock-out mice exhibit abnormal development of facial profile, defective bone formation, and lysosomal storage disorder.
Lorne A Clarke, University of British Columbia
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).
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt exon 5 of the Idua gene. The construct was introduced into 129X1/SvJ X 129S1/Sv-derived R1 embryonic stem (ES) cells. Care was taken not to disrupt the closely linked Sfat sulfate transporter gene. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice for at least 11 generations by the donating lab (see SNP results below).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 43 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Lorne A Clarke|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Idua, iduronidase, alpha-L|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|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.|
|Mutations Made By|| |
Lorne Clarke, University of British Columbia
When maintaining a live colony, homozygous mice may be bred together, however, the donating investigator reports that 21% of homozygous males and 40% of homozygous females live past 12 months of age.
When using the IDUA KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004068 in your Materials and Methods section.