B6.129-Dio1^tm1Vag/J

Stock number: 018984
Product name: D1KO
Research areas: Endocrine Deficiency Research, Metabolism Research

Description

These Dio1 knockout mice may be useful in applications involving hyperthyroidism, iodine deficiency, and metabolism regulation.

Detailed description

A neo cassette replaces exon 2 of the deiodinase, iodothyronine, type I (Dio1) gene, including the TGA selenocysteine codon, abolishing gene function in these D1KO mice. D1 is a selenoenzyme expressed in the liver, kidney, thyroid, and pituitary where it generates triiodothyronine (T₃) thyroid hormone from thyroxine (T₄) for export to the plasma. D1 is also a scavenger enzyme, playing a role in iodide conservation in peripheral tissues and the thyroid. Homozygotes are viable and fertile. D1KO mice exhibit increased fecal excretion of iodothyronines and increased levels of T₄ and reverse (r)T₃ in serum.

Development

A targeting vector was designed to replace exon 2 of the deiodinase, iodothyronine, type I (Dio1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129-dervived DS2A embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to C57BL/6 females and subsequently a colony of D1KO mice were established. D1KO mice were then mated to D2KO mice deficient of the deiodinase, iodothyronine, type 2 (Dio2) gene. These double mutant mice were backcrossed for at least 10 generations to C57BL/6 mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation and the D1KO and D2KO alleles were separated. D2KO mice are maintained a Stock No. 018985.

Allele

Symbol: Dio1^tm1Vag
Name: targeted mutation 1, Valerie Anne Galton
MGI accession ID: MGI:3613031
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dio1
Marker name: deiodinase, iodothyronine, type I
Chromosome: 4
Strain of origin: 129
Molecular note: Exon two, containing the TGA selenocysteine codon, was replaced with the neo cassette. Protein activity was not detected in mutant liver, kidney, thyroid or pituitary tissues.
General note: ES cell line = DS2A