An ENU-induced mutation in the mouse Rnf212 gene is associated with male meiotic failure and infertility
Related Experiment Video
Updated: Apr 21, 2026
Transgenic Rodent Assay for Quantifying Male Germ Cell Mutant Frequency
Published on: August 6, 2014
Yasuhiro Fujiwara1, Hirokazu Matsumoto2, Kouyou Akiyama2
1Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Abstract:
The ENU-induced repro57 mutation was identified in an unbiased screen for the discovery of novel genes for fertility. Male repro57 homozygous mice are infertile and exhibit significantly reduced testis weight compared with WT mice. Histological examination of mutant testes revealed that spermatocytes degenerated during late prophase, and no mature spermatozoa were found in the seminiferous epithelium, suggesting that infertility is caused by the arrest of spermatogenesis at late meiotic prophase. Consistent with this hypothesis, the number of foci with MLH1, a protein essential for crossing over, is greatly reduced in repro57 mutant spermatocytes, which also lack chiasmata between homologs and exhibit premature dissociation of XY chromosomes. In repro57 mutant mice, we identified a mutation in the Rnf212 gene, encoding Ring finger protein 212. The overall phenotype of repro57 mice is consistent with the recently reported phenotype of the Rnf212 knockout mice; slight differences may be due to genetic background effects. Thus, the repro57 nonsense mutation provides a new allele of the mouse Rnf212 gene.
Insights
A novel mutation in the Ring finger protein 212 (Rnf212) gene causes male infertility in mice. This mutation disrupts spermatogenesis by impairing chromosome pairing and crossing over during meiosis.
Area of Science:
- Genetics
- Reproductive Biology
- Mouse Models
Background:
- Fertility is crucial for species propagation.
- Understanding the genetic basis of male infertility is essential for reproductive health.
- Novel gene discovery aids in elucidating complex biological processes.
Purpose of the Study:
- To identify novel genes involved in male fertility.
- To characterize the genetic and phenotypic effects of the repro57 mutation.
- To investigate the role of Rnf212 in spermatogenesis.
Main Methods:
- ENU mutagenesis screen for fertility defects.
- Phenotypic analysis of infertile mice (testis weight, histology).
- Meiotic analysis (MLH1 foci, chromosome pairing, chiasmata).
- Genetic mapping and sequencing to identify the causative mutation.
Main Results:
- The repro57 mutation leads to male infertility and reduced testis weight.
- Mutant mice exhibit spermatocyte degeneration during meiotic prophase.
- Reduced MLH1 foci, lack of chiasmata, and premature XY chromosome dissociation were observed.
- A nonsense mutation in the Rnf212 gene was identified as the cause of the repro57 phenotype.
Conclusions:
- The repro57 mutation is a novel allele of the mouse Rnf212 gene.
- Rnf212 is essential for successful spermatogenesis and male fertility.
- Disruption of Rnf212 function leads to meiotic arrest and infertility.
Related Concept Videos
03:09Meiosis I
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
01:16In-vitro Mutagenesis
01:21Nondisjunction
02:02Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
02:57Meiosis vs. Mitosis
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
02:27Nonsense-mediated mRNA Decay
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...