In these GRTH-/- mice, a neo cassette replaces exons 6-7 and part of exon 5 of the (Ddx25) gene, abolishing gene expression. These mice may be useful for studying spermiogenesis and male infertility.
Maria Dufau, NIH
GRTH-/- mice contain a neo cassette replacing exons 6-7 and part of exon 5 of the DEAD (Asp-Glu-Ala-Asp) box polypeptide 25 (Ddx25) gene, abolishing gene expression. Ddx25, also known as gonadotropin-regulated testicular RNA helicase (GRTH), is a testis-specific posttranscriptional regulator of genes that are essential for spermatid elongation and completion of spermiogenesis. GRTH is expressed in both somatic Leydig cells and germ cells. Female GRTH-/- are fertile. Male homozygotes are sterile with azoospermia caused by a complete arrest of at step 8 spermiogenesis, which results in the failure of round spermatids to elongate. Males display normal gonadotropin and androgen profiles.
A targeting vector was designed in the laboratory of Dr. Maria L Dufau (Molecular Endocrinology NICHD, NIH) to replace exons 6-7 and part of exon 5 encoding the DEAD (Asp-Glu-Ala-Asp) box polypeptide 25 (Ddx25) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6N to generate a colony of GRTH-/- mice. These mice were bred to C57BL/6N mice for at least 15 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Maria L Dufau|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ddx25, DEAD (Asp-Glu-Ala-Asp) box polypeptide 25|
|Strain of Origin||129S4/SvJae|
|Molecular Note||This allele contains a mutation in the second ATG codon in exon 5, partial deletion of exon 5, and complete deletion of exons 6-7, which contain the conserved ATPase motif, G-GKT, and the PTRELA motif of the RNA helicase family. PCR analysis confirmed recombination and Northern and Western blot indicated lack of transcript and protein in mutant testes.|
When maintaining a live colony, homozygous females may be bred with heterozygous, wildtype, or C57BL/6NJ males (Stock No. 005304). Homozygous males are sterile.
When using the B6N.129S4-Ddx25tm1Mld/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024751 in your Materials and Methods section.