Xylt1npo ENU-induced mutant mice possess a missense mutation in the xylosyltransferase 1 gene making them useful when studying chondrocyte maturation and mammalian dwarfism.
Scott Weatherbee, Yale University School of Medicine
These Xylt1npo ENU-induced mutant mice possess a missense mutation in the xylosyltransferase 1 (Xylt1) gene, affecting an evolutionarily conserved residue. XYLT1 is localized to the Golgi where it catalyzes a rate-limiting step in the addition of glycosaminoglycan side chains to proteoglycans, which is critical for proteoglycan function within the extracellular matrix. XYLT1 is specifically expressed in chondrocytes during embryonic development. These pug mice are viable and semi-fertile. Homozygotes are viable but few survive long enough to be weaned due to competitive disadvantage with larger littermates. Pug mice retain 15% xylosyltransferase 1 activity. They display premature ossification of long bones resulting in a dwarf phenotype. Bones of these mice exhibit premature maturation and early ossification, which leads to disproportionate dwarfism. Bones in these mice show a 20% length reduction compared to WT mice. They display an increase in intrabecular bone volume with no change in cortical bone volume or density.
Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify a family of “pug” mice exhibiting shorter limbs E18.5 compared to littermates. Using a candidate gene approach the mutation was identified and mapped to the xylosyltransferase 1 (Xylt1) gene on Chromosome 7. Sequencing of these genes identified a T to A transversion (T2794A) in Xylt1 resulting in an arginine for tryptophan missense mutation at amino acid position 932 (W932R). Pug mice were bred to FVB/NJ mice for at least 10 generations. Upon arrival The Jackson Laboratory, mice were bred to FVB/NJ (Stock No. 001800) for at least one generation to establish the colony.
|Allele Type||Chemically induced (ENU) (Hypomorph)|
|Gene Symbol and Name||Xylt1, xylosyltransferase 1|
|Strain of Origin||C57BL/6J|
|Molecular Note||ENU induced a point mutation (T to A) that results in the missense amino acid substitution of arginine for tryptophan at position 932 (W932R). This mutation results in a failure of the product to localize to the cis-Golgi. Expression of the mutant protein in a cell line results in reduced enzymatic activity.|
When maintaining a live colony heterozygous mice may be bred to wildtype mice from the colony or to FVB/NJ inbred mice (Stock No. 001800). The donating investigator reports that few homozygous mice survive to weaning.
When using the FVB.B6-Xylt1npo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025435 in your Materials and Methods section.