These Naglu knock-out mice exhibit massive accumulation of heparan sulfate in liver and kidney and vacuolation in many cells, including macrophages, epithelial cells, and neurons.
Elizabeth F. Neufeld, UCLA School of Medicine
At birth, homozygous null mice are viable, normal in size, and do not display any gross physical or behavioral abnormalities. The lysosomal enzyme alpha-N-acetylglucosaminidase (Naglu) is absent in all tissues. Large amounts of heparan sulfate accumulate in liver and kidney, and lesser amounts in other organs. At one month of age, vacuolated macrophages can be found in most tissues. Epithelial cells in kidney and neurons in some parts of the brain are also affected. The vacuolation becomes more prominent with age. At 4-5 months, the mice show abnormal behavior in an open field test. The life span is 8-12 months. Older animals may have urinary retention and difficulty walking and must be euthanized. The null mice were originally described as fertile, but their fertility has decreasd markedly with repeated back-crossing to an inbred strain. These mice are suitable for examining the pathophysiology of the Sanfilippo syndrome type B and for developing therapies for this lysosomal storage disorder.
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter and a Herpes simplex virus thymidine kinase gene driven by its own promoter was used to disrupt a portion of exon 6. The construct was electroporated into 129S6/SvEv-derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6 females.
|Allele Name||targeted mutation 1, Elizabeth F Neufeld|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||MPS IIIB; Naglu-|
|Gene Symbol and Name||Naglu, alpha-N-acetylglucosaminidase (Sanfilippo disease IIIB)|
|Strain of Origin||129S/SvEv-Gpi1c|
|Molecular Note||Exon 6 of this gene, a region known to harbor several Sanfilippo B mutations, was disrupted by the insertion of a neomycin resistance gene via homologous recombination. Protein from homozygous mutant animals was negative for enzyme activity.|
|Mutations Made By|| |
Elizabeth Neufeld, UCLA School of Medicine
This strain originated on a B6;129S6 background and has been backcrossed to C57BL/6J for ten generations(9/2000). The donating investigator maintains this mutant strain by backcrossing to C57BL/6 animals. Coat color expeced from breeding:Black
When using the Naglu- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003827 in your Materials and Methods section.