AR-NC transgenic mice express a mouse Ar gene carrying a C556G substitution and an EGFP as a marker of transgene expression. The substitution inhibits DNA binding and blocks classical (C) testosterone signaling allowing only non-classical (NC) signaling. This strain may be useful for studies of male reproductive development.
A companion strain, AR-C, is modified to inhibit non-classical signaling, and is available as Stock No. 036469.
William Walker, University of Pittsburgh
Ar (androgen receptor) encodes a nuclear receptor superfamily member that is expressed in Sertoli cells and becomes activated by binding to the testicular androgens, testosterone or its metabolite, dihydrotestosterone. AR is required for male embryonic sexual differentiation, the development of male sexual characteristics, and the regulation of spermatogenesis. Androgens interact with the androgen receptor through two separate pathways: classical and nonclassical. The classical pathway involves interaction of the receptor-ligand complex with androgen response elements in the nucleus and effects gene expression. The non-classical pathway involves interaction of the receptor-ligand complex with Src kinase at the plasma membrane and affects cell function and gene expression.
AR-NC transgenic mice express a modified mouse Ar gene and an EGFP that functions as a marker for transgene expression. Ar is modified to have a C556G substitution. The substitution inhibits DNA binding and blocks classical testosterone signaling. Mice hemizygous for the transgene are viable and fertile with no apparent phenotype, the viability/fertility of homozygotes has not been assessed.
When AR-NC mice are combined with a conditional Ar knockout (for example, Artm2.1Reb, Stock No. 018450) and mice carrying a Cre recombinase with widespread expression (for example, Tg(Sox2-cre)1Amc, Stock No. 008454) male progeny have an anogenital distance similar to females, reduced testicular weight, increased levels of luteinizing hormone, and cannot produce sperm (spermatogenesis is arrested early in meiosis). This strain may be useful for studies of male reproductive development.
Of interest, AR-C (Tg(Ar*,-EGFP)NCWhw) transgenic mice, which are modified to inhibit classical signaling, are available as Stock No. 036469.
The bacterial artificial chromosome, BAC-236EGFP, containing the 167 kb mouse sequence of the Ar gene and approximately 40 kb each of the 5’ and 3’ flanking sequence was modified to include a C556G substitution (cysteine to glycine) in exon 2 and insert an IRES, EGFP and polyA site after the Ar stop codon. The substitution is placed in the DNA binding domain and inhibits DNA binding and classical testosterone signaling. This BAC was microinjected into the pronuclei of fertilized C57BL/6J oocytes. Founder line 2.77 (NC non-classical) was bred to C57BL/6J mice. Mice were then bred to other unspecified strains (cre and floxed) on unknown backgrounds. There are 1-2 copies of the transgene. 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).
|Allele Name||transgene insertion NC, William H Walker|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Gene Symbol and Name||Tg(Ar*C556G,-EGFP)NCWhw, transgene insertion NC, William H Walker|
|Strain of Origin||C57BL/6|
|Molecular Note||This transgene includes a 167 kb genomic mouse Ar gene and approximately 40 kb each of 5' and 3' flanking sequence. An IRES, EGFP reporter gene, and poly A site are present after the stop codon for Ar to coexpress AR and EGFP. There is a one base pair mutation in exon 2 resulting in a C556G amino acid change in the mouse AR protein.|
Hemizygotes are viable and fertile. The viability/fertility of homozygotes has not been assessed.
When using the AR-NC mouse strain in a publication, please cite the originating article(s) and include JAX stock #036595 in your Materials and Methods section.