MPSII KO mice may be useful for studying and developing potential therapies for treating Hunter syndrome.
Joseph Muenzer, University of North Carolina at Chapel Hill
MPSII KO mice have a neo cassette replacing exon 4 and part of exon 5 of the X-linked iduronate 2-sulfatase (Ids) gene, abolishing gene expression. Lysosomal accumulation of glycosaminoglycans (GAG) causes chronic and progressive cell and tissue damage leading to organ dysfunction as seen in a group of disorders called mucopolysaccharidoses (MPSs). MPSII, also known as Hunter syndrome, is an X-linked error of metabolism that is specifically caused by a deficiency in IDS, a lysozomal enzyme responsible for the catabolism and removal of dermatan and heparan sulfate GAGs. Heterozygous females are viable and fertile. Hemizygous males show progressive onset of skeletal and neurological disease by three months of age and die by 60-70 weeks of age due to secondary CNS disease. Urinary GAG levels are four-fold higher in these KO mice by 6 weeks of age. GAG accumulation is evident in the liver, kidney, lung, spleen, skeletal muscle, and heart. At 60 weeks, tissue vacuolization is wide spread, including heart valves, testes and cerebellar neurons. Neuronal necrosis of the brainstem and spinal cord are also evident. Skeletal abnormalities, such as thickened digits, swollen hocks, and distorted craniofacial bones, are evident, and KO mice are significantly smaller than wildtype littermates by 10 weeks of age. These mice exhibit alopecia, and they perform poorly in open-field tests and have severely compromised walking patterns. Homozygous mice are perinatal lethal.
A targeting vector was designed to replace exon 4 and part of exon 5 encoding the X-linked iduronate 2-sulfatase (Ids) gene with a neomycin resistance (neo). The construct was electroporated into embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to B6D2 females. Carrier females have been crossed for at least 18 generations to C57BL6NTac males. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Joseph Muenzer|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||ids-; MPSII|
|Gene Symbol and Name||Ids, iduronate 2-sulfatase|
|Strain of Origin||Not Specified|
|Molecular Note||A targeting vector was designed to replace exon 4 and part of 5 with a neomycin resistance gene.|
These mice contain an X-linked mutation. When maintaining a live colony, heterozygous females are bred to wildtype males from the colony or to C57BL/6NJ males (Stock No. 005304). Hemizygous males show progressive onset of skeletal and neurological disease at 3-4 months of age and die by 60-70 weeks of age due to secondary CNS disease. Homozygous mice are perinatal lethal.
When using the IdS-KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #024744 in your Materials and Methods section.