This THTR-2- knockout mouse line has a deletion of exons 1-2 of the Slc19a3 gene. These mice may be useful in studying the role of thiamin transporters in regulating thiamin homeostasis in different cells; including liver and kidney cells.
Hamid M Said, University of California, Irvine
The THTR-2- knockout mutation has exons 1-2 of the thiamin transporter-2 gene (ThTr2 or Slc19a3) replaced by a neo cassette. No mRNA or protein expression is observed in intestinal tissues. Homozygous mice (THTR-2-/-) are viable and fertile as younger mice. THTR-2-/- mice exhibit significant decreases in both intestinal thiamin uptake and plasma thiamin levels. No changes in blood biotin, glucose, or insulin levels are reported for homozygotes. The expression of thiamin transporter-1 (THTR-1) is normal in intestine, but increased in kidney, in THTR-2-deficient mice. Homozygotes become lethargic around nine months of age, with cachexia/progressive wasting and eventually premature death by ~12 months of age. Histologic examination at nine months of age reveals increased incidence of both liver defects (hepatic parenchyma injury, necrosis, and chronic inflammation) and kidney defects (interstitial chronic inflammation of the renal cortex, degeneration of the proximal convoluted tubules, and arteriosclerosis/renal nephosclerosis).
A targeting vector was designed to replace exons 1-2 (including the ATG transcriptional start site) of the thiamin transporter-2 gene (ThTr2 or Slc19a3) with a neomycin cassette. The construct was electroporated into undisclosed embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric animals were bred with C57BL/6J mice to establish the colony. Mice heterozygous for the THTR-2- allele were then bred together for several generations (always with black coat color) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Hamid M Said|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Slc19a3tm1Igl; Slc19a3tm1Itl|
|Gene Symbol and Name||Slc19a3, solute carrier family 19, member 3|
|Strain of Origin||Not Specified|
|Molecular Note||A neo cassette replaced exons 1 and 2. The absence of protein expression was confirmed by western blot analysis on intestine extracts.|
|Mutations Made By|| |
Hamid Said, University of California, Irvine
When maintaining a live colony, heterozygous mice may be bred together or with wildtype mice from the colony. While homozygous mice are viable and fertile as younger mice, they become lethargic around nine months of age, with cachexia/progressive wasting and eventually premature death by ~12 months of age.
When using the STOCK Slc19a3tm1Said/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017343 in your Materials and Methods section.