These Dio2 knockout mice may be useful in applications involving thyroid hormone homeostasis, metabolism regulation, and bone strength.
Valerie Anne Galton, Dartmouth Medical School
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Dio2 | deiodinase, iodothyronine, type II |
A neo cassette replaces sequence including the 5' end of exon 2 of the deiodinase, iodothyronine, type 2 (Dio2) gene. The replaced sequence includes the TGA selenocysteine codon, removal of which abolishes gene function in these D2KO mice. D2 is a selenoenzyme expressed mainly in the pituitary, brown adipose tissue (BAT) and brain where it generates local triiodothyronine (T3) thyroid hormone. Homozygotes are viable and fertile. D2KO mice exhibit deficits in thyroid stimulating hormone (TSH) regulation, thermogenesis, and auditory function. Brain T3 content is reduced while brain thyroxine (T4) content is elevated. The bones of D2KO mice are more brittle and fracture easier. They show a reduction in bone formation and an increase in skeletal mineralization.
A targeting vector was designed to replace sequence, including the 5' end of exon 2, of the deiodinase, iodothyronine, type 2 (Dio2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2-dervived AB2.2 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 D2KO mice were established.
D2KO mice were then mated to D1KO mice deficient of the deiodinase, iodothyronine, type I (Dio1) 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. D1KO mice are maintained a Stock No. 018984.
Allele Name | targeted mutation 1, Valerie Anne Galton |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | D2KO; Dio2- |
Gene Symbol and Name | Dio2, deiodinase, iodothyronine, type II |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 12 |
Molecular Note | A neomycin selection cassette replaced a 2.6kb region including a 5' portion of exon 2. 72% of the coding region was deleted, including a TGA codon that encodes the selenocysteine located at the active site. Northern blot analysis of total RNA obtained from brown adipose tissue showed an absence of transcript in homozygous mutant mice. Functional ablation of the endogenous protein in homozygous mutant mice was confirmed by assaying deiodination in brown adipose tissue. |
Mutations Made By | Valerie Anne Galton, Dartmouth Medical School |
When maintaining a live colony, homozygous mice may be bred together.
When using the D2KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #018985 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Dio2<tm1Vag> |
Frozen Mouse Embryo | B6.129-Dio2<tm1Vag>/J | $2595.00 |
Frozen Mouse Embryo | B6.129-Dio2<tm1Vag>/J | $2595.00 |
Frozen Mouse Embryo | B6.129-Dio2<tm1Vag>/J | $3373.50 |
Frozen Mouse Embryo | B6.129-Dio2<tm1Vag>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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