Homozygous Hormad1 knockout mice are infertile. Testes exhibit meiotic arrest at the pachytene stage and oocytes arrest at the blastocyst stage. These mice may be useful in studying synaptonemal complex formation, recombination and chromosome segregation in meiosis.
Aleksandar Rajkovic, Magee Womens Research Institute
Hormad1 is a germ cell specific HORMA domain encoding gene that is a critical component of the axial elements of the synaptonemal complex. The Hormad1 knockout allele has a neo cassette replacing exons 4 and 5 of the gene. Male and female mice homozygous for the mutation are infertile. Testes from adult mutant males are small; seminiferous tubules are hypocellular and contain no post-meiotic germ cells such as spermatids and spermatozoa. The synaptonemal complex normally visible at the pachytene stage cannot be detected in 2 week old mutant spermatocytes resulting in meiotic arrest. In females, HORMAD1 deficiency causes disruption of second metaphase in oocytes (mis-orientation of chromatid attachment to spindle), aneuploidy in 2-cell and 8-cell embryos, arrest at the blastocyst stage, early embryo death, and failure of implantation.
These mice may be useful in studying synaptonemal complex formation, recombination and chromosome segregation in meiosis.
A targeting vector was designed by Dr. Aleksander Rajkovic (Magee Women’s Research Institute – University of Pittsburgh) to replace exons 4 and 5 of the HORMA domain containing 1 gene (Hormad1) on chromosome 3 with a neomycin cassette. Removal of exons 4 and 5 causes a frameshift mutation resulting in absence of transcript, although a faint low molecular weight band representing mutant transcript is visible. The construct was electroporated into 129S7/SvEvBrd-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6 females to establish the colony. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Aleksandar Rajkovic|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Hormad1, HORMA domain containing 1|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||Exons 4 and 5 were replaced with a neomycin resistance gene. Small amounts of truncated RNA transcripts were detectable on RT-PCR, and Western blot analysis on testis extracts showed absence of the protein.|
While maintaining a live colony, these mice are bred as heterozygotes. Male and female mice homozygous for the mutation are not fertile.
When using the Hormad1- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41469 in your Materials and Methods section.