B6.Cg-Ghrhr^tm1.1Deh Trhr^tm1.1Deh Tg(CAG-cre/Esr1*)5Amc/Deh

Stock number: 036337
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

This strain carries loxP-flanked conditional-ready alleles for both Ghrhr and Trhr, which are valuable in characterizing thyroid function, along with the tamoxifen-inducible Tg(CAG-cre/Esr1*)5Amc is segregating hemizygous and wildtype in this strain. These loxP-flanked alleles are also available on a 129S genetic background in Stock No. 036336.

Detailed description

This strain carries loxP-flanked conditional-ready alleles for both Ghrhr and Trhr, which are valuable in characterizing thyroid function, along with the tamoxifen-inducible Tg(CAG-cre/Esr1*)5Amc is segregating hemizygous and wildtype in this strain. These loxP-flanked alleles are also available on a 129S genetic background in Stock No. 036336). In the absence of cre activity these mice have a normal phenotype.

Development

The Trhr^tm1Deh allele, which has a loxP site upstream of exon2 and an FRT-flanked neomycin selection cassette followed by a loxP site downstream of exon 2, was generated in 129S1/SvImJ-derived ES cells. The founder was bred both to 129S1/SvImJ and separately to C57BL/6J. The C57BL/6J outcrossed mice were backcrossed onto C57BL/6J until generation N9 before a cross to B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/RainJ to excise the neomycin selection cassette. The resulting strain was bred to B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J.

The Ghrhr^tm1Deh allele, which has a loxP site upstream of exon 2 and an FRT-flanked neomycin selection cassette and loxP site downstream of exon 3, was generated in C57BL/6N-A^tm1Brd derived JM8.A3 ES cells. This allele was backcrossed onto C57BL/6J for four generations then bred to B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/RainJ to excise the neomycin selection cassette then backcrossed several more generations to C57BL/6J to generate B6J.B6N(129S4)-Ghrhr^tm1.1Deh/Deh strain. The B6J.B6N(129S4)-Ghrhr^tm1.1Deh/Deh and B6.Cg-Trhr^tm1.1Deh Tg(CAG-cre/Esr1*)5Amc/Deh strains were intercrossed when each was at generation NE9 to generate this strain, which was intercrossed to homozygosity for both Ghrhr^tm1.1Deh and Trhr^tm1.1Deh and segregating for Tg(CAG-cre/Esr1*)5Amc/Deh. Cryorecovery from frozen sperm will generated mice heterozygous for both conditional-ready alleles and segregating hemizygous or wiltype for Tg(CAG-cre/Esr1*)5Amc.

Allele

Symbol: Tg(CAG-cre/Esr1*)5Amc
Name: transgene insertion 5, Andrew P McMahon
MGI accession ID: MGI:2182767
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: CAG-CreEr; CAGG-Cre; CaggCreER; CAGGCre-ER; CAGGCre-ER^TM; CAGGCre-ERtm line 5.8; CAGGS-CreER; CAGGS-CreErT; CMV-creERT; Cre-ER; Cre-ER^TM; CreESR^T; ER-cre; Tg(CAG-cre/Esr1)5Amc; Tg(cre/Esr1)5Amc; Tg:Cag-Cre/Esr1; Tg^CreER; TgCAGGCreER; uCreER^T; CAG-Cre
Marker symbol: Tg(CAG-cre/Esr1*)5Amc
Marker name: transgene insertion 5, Andrew P McMahon
Marker synonyms: CAG-CreERT2; CAGGCre-ER; CAGGCre-ER^TM; CAGG-CreERT2; CAGGCre-ERtm line 5.8; CAGGS-CreER; CAGGS-CreErT; CMV-creERT; Cre-ER; Cre-ERTM; ER-cre; Tg(CAG-cre/Esr1)5Amc; Tg(cre/Esr1)5Amc
Chromosome: UN
Strain of origin: (C57BL/6 x CBA)F1
Expressed genes: cre/Esr1,Cre recombinase and estrogen receptor 1 fusion gene,
Site of expression: tamoxifen-inducible cre; widespread pattern of expression; tamoxifen administration will also induce Cre recombination in developing embryos of treated mothers and in cultured cells derived from transgenic mice
Molecular note: This transgene expresses a fusion protein consisting of Cre recombinase joined to the ligand-binding domain of a mouse estrogen receptor modified to bind to 4-hydroxytamoxifen, but not to endogenous estrogen. The CAG promoter, containing a chicken beta actin promoter/enhancer coupled with the cytomegalovirus immediate-early (CMV-IE) enhancer, drives high levels of expression in most tissues. In the presence of tamoxifen, the fusion protein is transported into the nucleus, where cre can excise loxP-flanked segments from conditionally modified genes.
General note: Homozygous transgenic mice are not viable or fertile. Hemizygous transgenic mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

In transgenic mice the mutant mouse estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the Cre/Esr1 fusion protein can only gain access to the nuclear compartment after exposure to tamoxifen. When crossed with a strain containing loxP sites flanking a sequence of interest, tamoxifen induced, Cre-mediated targeted deletions are generated in the offspring. Tamoxifen administration will induce Cre recombination in developing embryos of treated mothers and in cultured cells derived from transgenic mice.

Note that this transgene does not contain the cre/ERT2 fusion but was mistakenly referred to by the synonym CAG-CreERT2 in publication. J:136965

Note that this transgene does not contain the cre/ERT2 fusion but was mistakenly referred to by the synonym CAGG-CreERT2 in publication. J:130851

Allele

Symbol: Trhr^tm1.1Deh
Name: targeted mutation 1.1, David E Harrison
MGI accession ID: MGI:7737669
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Trhr
Marker name: thyrotropin releasing hormone receptor
Marker synonyms: CHNG7; TRH-R; TRH-R1
Chromosome: 15
Strain of origin: 129S1/SvImJ
Molecular note: The frt-flanked neomycin selection cassette was excised from the Trhr allele, yielding this conditional-ready allele that has exon 2 flanked with loxP sites.

Allele

Symbol: Ghrhr^tm1.1Deh
Name: targeted mutation 1.1, David E Harrison
MGI accession ID: MGI:7737684
Generation method: Endonuclease-mediated
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Ghrhr
Marker name: growth hormone releasing hormone receptor
Marker synonyms: Ghrfr; GHRHREC; GRFR; IGHD1B; IGHD4
Chromosome: 6
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The frt-flanked neomycin selection cassette was excised from the Ghrhr allele, yielding this conditional-ready allele that has exons 2 and 3 flanked with loxP sites.