This strain may be useful for studying the regulation of meiotic entry and meiotic sex chromosome inactivation in germ cells by small RNA pathways.
Paula Cohen, Cornell University
These AGO4-/- mice lack exons 3-17 of the argonaute RISC catalytic subunit 4 (Ago4) gene. This gene encodes one of the four Argonaute genes which are essential for processing of small RNAs in multiple RNA interference pathways. Ago4 is mainly expressed in the testis, specifically localized to the XY body during meiotic prophase I. Homozygous females and heterozygous males are viable and fertile, while homozygous males are subfertile. Males exhibit severely reduced fertility associated with premature entry of male germ cells into meiosis, and silencing defects in the XY body during meiosis. They have reduced testis size, lower sperm counts, and exhibit an increase in apoptotic cells within the prophase I layers of the seminiferous epithelium.
A targeting vector was designed to insert a loxP site upstream of exon 3, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of exon 17 of the argonaute RISC catalytic subunit 4 (Ago4) gene. The construct was electroporated into 129P2-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred together. Offspring were bred with B6.129S4-Gt(ROSA)26Sor
|Allele Name||targeted mutation 1.1, Paula E Cohen|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ago4, argonaute RISC catalytic subunit 4|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A loxP site was inserted in intron 2 and an FRT flanked pgk-neo cassette and loxP site were inserted into intron 17 via homologous recombination. Recombinase mediated recombination removed exons 3-17 and the neo cassette.|
When maintaining a live colony, homozygous females may be bred to heterozygous males from the colony. Homozygous males are subfertile.
When using the B6.129P2(Cg)-Ago4tm1.1Peco/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021335 in your Materials and Methods section.