B6;129-Rxra^tm1.1Neg/J

Stock number: 034538
Product name: Rxra^T167A , Rxrα^T167A
Research areas: Diabetes and Obesity Research, Metabolism Research

Description

Rxra^T167A mice carry a point mutation in an evolutionarily conserved motif, which renders the site incapable of phosphorylation. Mice homozygous for this retinoid X receptor alpha T167A mutation display a diminished response to dietary restriction, and may be useful for studying the regulation of energy metabolism.

Detailed description

In mice, threonine 167 (162 in humans) is an evolutionarily conserved phosphorylation motif of the retinoid X receptor α (Rxra) gene, involved in the regulation of energy metabolism. These knock-in mice carry the T167A mutation in the Rxra gene, which nullifies this critical phosphorylation site. Mice carrying this mutation show altered expression of numerous genes in canonical metabolic pathways across muscle, liver, and adipose tissues in response to dietary challenges. Moreover, mice homozygous for the T167A mutation exhibit normal bodyweight, but reduced decreases in blood glucose and altered lipid metabolism in white adipose tissue under fasting conditions. Both heterozygous and homozygous mice are viable and fertile with normal breeding.

Development

The Rxra^T167A allele was created in the laboratory of Dr. Masahiko Negishi at the National Institute of Environmental Health Sciences. A targeting vector containing an ACN self-excising loxP-flanked neomycin cassette and a diptheria toxin (DTA) gene was used to replace the threonine residue at position 167 with an alanine residue. The left homology arm included all of exons 2, 3, and 4 (including the T167A substitution codon in exon 4), while the right homology arm contained part of intron 4. The construct was electroporated into (129S6/SvEvTac x C57BL/6NCrl)F1-derived Nagy-G4 embryonic stem (ES) cells. In contrast to the original publication describing these mice, the donating investigator reports the chimeric males were crossed with B6(Cg)-Tyr^c-2J/J females (Stock No. 000058) for germline transmission and for self-excision of the ACN cassette. The resulting progeny were subsequently interbred to produce homozygotes prior to sending albino males to The Jackson Laboratory Repository in 2020. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
Of note, The Jackson Laboratory will maintain this colony by breeding black mice together, but they may be segregating for the Tyr^c-2J (albino) allele.

Allele

Symbol: Rxra^tm1.1Neg
Name: targeted mutation 1.1, Masahiko Negishi
MGI accession ID: MGI:6383951
Generation method: Targeted
Attributes: Not Applicable
Synonyms: Rxra^T167A
Marker symbol: Rxra
Marker name: retinoid X receptor alpha
Marker synonyms: 9530071D11Rik; NR2B1; RXR alpha 1; RXRalpha; RXR-alpha; RXRalpha1
Chromosome: 2
Strain of origin: (129S6/SvEvTac x C57BL/6NCrl)F1
Molecular note: A targeting vector containing an ACN self-excising loxP-flanked neomycin cassette and a diptheria toxin (DTA) gene was used to replace the threonine residue at position 167 with an alanine residue. The left homology arm included all of exons 2, 3, and 4 (including the T167A substitution codon in exon 4), while the right homology arm contained part of intron 4.