These Fkbp4 (or FKBP52) knockout mice are viable as homozygotes, but not fertile. They may have applications in studies related to androgen, progesterone, and glucocorticoid receptor signaling pathways and reproduction.
Sudhansu Dey, Cincinnati Children's Hospital
FKBP4 (or FKBP52) is a member of the immunophilin protein family and is known to play a role in protein folding and trafficking. FKBP4 functions as a co-chaperone that binds to HSP90 in steroid receptor complexes. In this strain the targeted allele lacks the entire Fkbp4 coding region. Homozygous mice are viable, but are not fertile. Male mice exhibit mild to severe hypospadia, ambiguous external genitalia, malformed seminal vesicles and a small-to-absent anterior prostate gland. Spermatozoa have reduced motility and fertilization efficiency. The donating investigator reports that homozygous females are infertile due to implantation failure. This strain may be useful for studying androgen, progesterone, and glucocorticoid receptor signaling pathways and reproduction.
A targeting vector was designed to exchange a neomycin selection cassette for the entire coding region (exons 1-10, approximately 9 kb) of the Fkbp4 (FKBP52) gene. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred C57BL/6 mice. The strain was maintained at the Mayo Clinic and then transferred to the laboratory of Dr. Sudhansu Dey. The Fkbp4 allele was introgressed into an outbred CD-1 background and has been maintained on the CD-1 (Crl:CD1) background for many generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, David F Smith|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||52KO; Fkbp52-|
|Gene Symbol and Name||Fkbp4, FK506 binding protein 4|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A neomycin resistance gene replaced the entire coding sequence. Western blot failed to detect protein in thymic cytosol of mutants.|
While maintaining a live colony, these mice are bred as heterozygotes. Heterozygote x heterozygote matings produce 50% fewer homozygotes the expected Mendelian ratio. Mice homozygous for the mutation are infertile.
When using the STOCK Fkbp4tm1Dvds/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017990 in your Materials and Methods section.
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