Generation of a novel mouse strain with conditional, cell‐type specific, expression of DND1

Nunez, Lisa; Mokkapati, Sharada; Yu, Cheng-Tai; Deng, Jian Min; Behringer, Richard R.; Matin, Angabin

doi:10.1002/dvg.23335

Cited by 2 publications

(1 citation statement)

References 31 publications

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“…Mouse alleles that overexpress DND1 have also been generated. The LSL-FM-Dnd1 flox 'knock-in' allele allows Cre recombinase-mediated expression of genetically engineered, FLAG-and myc-tagged DND1 in a cell-type-specific manner [59]. The role of this allele in cancer remains to be tested.…”

Section: Genetically Engineered Mouse Alleles Of Dnd1mentioning

confidence: 99%

The Role of DND1 in Cancers

Zhang

Godavarthi

Williams-Villalobo

et al. 2021

Cancers

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The Ter mutation in Dead-End 1 (Dnd1), Dnd1Ter, which leads to a premature stop codon, has been determined to be the cause for primordial germ cell deficiency, accompanied with a high incidence of congenital testicular germ cell tumors (TGCTs) or teratomas in the 129/Sv-Ter mice. As an RNA-binding protein, DND1 can bind the 3′-untranslated region (3′-UTR) of mRNAs and function in translational regulation. DND1 can block microRNA (miRNA) access to the 3′-UTR of target mRNAs, thus inhibiting miRNA-mediated mRNA degradation and up-regulating translation or can also function to degrade or repress mRNAs. Other mechanisms of DND1 activity include promoting translation initiation and modifying target protein activity. Although Dnd1Ter mutation causes spontaneous TGCT only in male 129 mice, it can also cause ovarian teratomas in mice when combined with other genetic defects or cause germ cell teratomas in both genders in the WKY/Ztm rat strain. Furthermore, studies on human cell lines, patient cancer tissues, and the use of human cancer genome analysis indicate that DND1 may possess either tumor-suppressive or -promoting functions in a variety of somatic cancers. Here we review the involvement of DND1 in cancers, including what appears to be its emerging role in somatic cancers.

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Section: Genetically Engineered Mouse Alleles Of Dnd1mentioning

confidence: 99%

The Role of DND1 in Cancers

Zhang

Godavarthi

Williams-Villalobo

et al. 2021

Cancers

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A transgenic DND1GFP fusion allele reports in vivo expression and RNA-binding targets in undifferentiated mouse germ cells

Ruthig

Yokonishi

Friedersdorf

et al. 2021

Biology of Reproduction

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In vertebrates, the RNA binding protein (RBP) Dead End 1 (DND1) is essential for primordial germ cell (PGC) survival and maintenance of cell identity. In multiple species, Dnd1 loss or mutation leads to severe PGC loss soon after specification or, in some species, germ cell transformation to somatic lineages. Our investigations into the role of DND1 in PGC specification and differentiation have been limited by the absence of an available antibody. To address this problem, we used CRISPR/Cas9 gene editing to establish a transgenic mouse line carrying a DND1GFP fusion allele. We present imaging analysis of DND1GFP expression showing that DND1GFP expression is heterogeneous among male germ cells (MGCs) and female germ cells (FGCs). DND1GFP was detected in MGCs throughout fetal life but lost from FGCs at meiotic entry. In postnatal and adult testes, DND1GFP expression correlated with classic markers for the pre-meiotic spermatogonial population. Utilizing the GFP-tag for RNA immunoprecipitation (RIP) analysis in MGCs validated this transgenic as a tool for identifying in vivo transcript targets of DND1. The DND1GFP mouse line is a novel tool for isolation and analysis of embryonic and fetal germ cells, and the spermatogonial population of the postnatal and adult testis.

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Generation of a novel mouse strain with conditional, cell‐type specific, expression of DND1

Cited by 2 publications

References 31 publications

The Role of DND1 in Cancers

The Role of DND1 in Cancers

A transgenic DND1GFP fusion allele reports in vivo expression and RNA-binding targets in undifferentiated mouse germ cells

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