Sex control by Zfy siRNA in the mouse

Peng, Qiang; Li, Ren-Yan; Jia, Bin; Li, Hongtao

doi:10.1016/j.theriogenology.2011.03.002

Cited by 6 publications

(2 citation statements)

References 17 publications

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“…They are widely used in biology, pharmacology, toxicology and other areas of scientific research in China (6–11). Chinese scientist detected Kunming mice in one of the heterozygous breeding females (12–16). In our study, we found that Kunming female species after breeding can develop spontaneous breast cancer in 10–12 months (average 11.5 months).…”

Section: Introductionmentioning

confidence: 99%

A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer

Zheng

Zhou²,

Meng

et al. 2014

International Journal of Oncology

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Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women.

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Section: Introductionmentioning

confidence: 99%

A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer

Zheng

Zhou²,

Meng

et al. 2014

International Journal of Oncology

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“…At present, there are only a little research on Zfx gene silencing to make the sex shift of offspring, so the mechanism of action of Zfx in sperm is not clear. Some studies have shown that reducing the level of Zfx/Zfy mRNA expression will make the physiological function of X/Y sperm worse, which can influence offspring gender [14,17,[20][21][22]. Zfy is closely related to sperm head and tail formation and neck development [23], which is highly expressed between meiosis I and II.…”

Section: Discussionmentioning

confidence: 99%

The RNAi vecter construction and verification of the functions in sexual control of Cervus elaphus Zfx gene

Wei

Song

et al. 2019

Preprint

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Background: Zinc finger protein X-linked (Zfx) was regarded to be a sex determination factor, and plays a critical role in spermatogenesis. RNAi is an effective method of silencing Zfx/Zfy mRNA expression. However, there has been little research on the use of RNAi technology to control the sex of the offspring of Cervus elaphus. The objective of this study was first to explore an efficient method to alter the Cervus elaphus offspring sex-ratio by silencing the genes Zfx during spermatogenesis.Results: Three recombinant expression vectors pLL3.7/A, pLL3.7/B and pLL3.7/C were constructed to interrupt the Zfx gene. The results showed that the expression of Zfx mRNA was significantly silenced by pLL3.7/A (P < 0.01), compared with the control group. The group injected with pLL3.7/A produced 94 Cervus elaphus, including 68 males and 26 females. The male rates (72.34%) were significantly higher than the control groups (P < 0.01).Conclusions: Our experiment suggest that the Zfx gene plays a significant role in the process of X-sperm formation. Zfx siRNA may be a useful approach to control offspring sex in Cervus elaphus.

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RNAi as a tool to control the sex ratio of mouse offspring by interrupting Zfx/Zfy genes in the testis

Zhang

Jia

et al. 2017

Mamm Genome

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The objective of this study was to explore a novel method to alter the sex-ratio balance of mouse offspring by silencing the paralogous genes Zfx/Zfy (Zinc finger X/Y-chromosomal transcription factor gene) during spermatogenesis. Four recombined vectors PRZ1, PRZ2, PRZ3, and PRZ4 (RNAi-Ready-pSIREN-RetroQ-ZsGreen) were constructed for interrupting the Zfx gene. Additionally, a recombined vector Psilencer/Zfy-shRNA was constructed for interrupting the Zfy gene. Male mice were randomly divided into 8 groups, with 20 animals per group. Five groups of mice were injected with PRZ1, PRZ2, PRZ3, PRZ4, and Psilencer/Zfy-shRNA vectors, respectively. The three control groups were injected with an equal volume of physiological saline, empty RNAi-Ready-pSIREN-RetroQ-ZsGreen vector, and empty Psilencer/Zfy-shRNA vector, respectively. All groups were injected every 7 days for a total of four injections. Fourteen days after the fourth injection, 10 male mice from each group were mated individually with 10 females. Testicular tissue of 10 male mice in each group was collected, and the expression level of Zfx/Zfy mRNA was determined by qRT-PCR. Results showed that, compared with the empty RNAi-Ready-pSIREN-RetroQ-ZsGreen vector and the physiological saline group, expression of Zfx mRNA decreased significantly after injection of PRZ1 (p < 0.01), PRZ3 (p < 0.01), and PRZ4 (p < 0.01), and 78.75 ± 7.50% of the offspring were male in PRZ4 group, significantly higher than the offspring derived from the empty RNAi-Ready-pSIREN-RetroQ-ZsGreen vector and physiological saline group (p < 0.01). In the PRZ1 group, the expression of Zfx mRNA was also significantly lower (p < 0.01), but the male rate of offspring was not different (p > 0.05). Conversely, the expression of Zfy mRNA decreased significantly after injection of Psilencer/Zfy-shRNA (p < 0.01) and 31.00 ± 11.00% of the offspring were male, significantly lower than in the physiological saline group (p < 0.01). In conclusion, our findings show that RNAi-mediated disruption of Zfx/Zfy in mouse testis affected X/Y spermatogenesis. Additionally, results suggest that the paralogous genes Zfx/Zfy play an important role in the process of X and Y sperm development. The individual interference of Zfx/Zfy may predict the outcome of X and Y haploid sperms. Presented herein is an advanced method developed to control mouse X/Y spermatogenesis and sex ratio of offspring.

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Sex control by Zfy siRNA in the mouse

Cited by 6 publications

References 17 publications

A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer

A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer

The RNAi vecter construction and verification of the functions in sexual control of Cervus elaphus Zfx gene

RNAi as a tool to control the sex ratio of mouse offspring by interrupting Zfx/Zfy genes in the testis

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