Mutations in <i>Lyar</i> and <i>p53</i> are synergistically lethal in female mice

Wang, Guan; Fulkerson, Christopher M.; Malek, Reem; Ghassemifar, Sara; Snyder, Paul W.; Mendrysa, Susan M.

doi:10.1002/bdra.23048

Cited by 15 publications

(13 citation statements)

References 41 publications

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“…During the preparation of our manuscript, another study on Lyar-mutant mice generated by gene-trap insertion was reported (Wang et al, 2012). Similar phenotypes were observed in the mice with reduced LYAR expression, in that the mutant mice were viable and fertile.…”

Section: Discussionsupporting

confidence: 61%

“…Similar phenotypes were observed in the mice with reduced LYAR expression, in that the mutant mice were viable and fertile. Further genetic analyses showed that Lyar and p53 double-mutant female mice exhibited embryonic lethality, suggesting that there is a genetic interaction between the two genes during embryogenesis (Wang et al, 2012). Thus, it is possible that the alterations in molecular or cellular processes caused by Lyar deficiency could be limited by p53 or a p53-like factor during spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Expression and Function of the Testis-Predominant Protein LYAR in Mice

Lee

Jin

Choi

et al. 2013

Molecules and Cells

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Mammalian spermatogenesis is a complex process involving an intrinsic genetic program of germ cell-specific and -predominant genes. In the present study, we analyzed the Ly-1 reactive clone (Lyar) gene in the mouse. Lyar, which is known to be expressed abundantly in the testis, encodes a nucleolar protein that contains a LYAR-type C2HC zinc finger motif and three nuclear localization signals. We herein confirmed that Lyar is expressed predominantly in the testis, and further showed that this expression is specific to germ cells. Protein analyses with an anti-LYAR antibody demonstrated that the LYAR protein is present in spermatocytes and spermatids, but not in sperm. To assess the functional role of LYAR in vivo, we used a genetrap mutagenesis approach to establish a LYAR-null mouse model. Lyar mutant mice were born live and developed normally. Male mutant mice lacking LYAR were fully fertile and showed intact spermatogenesis. Taken together, our results demonstrate that LYAR is strongly preferred in male germ cells, but has a dispensable role in spermatogenesis and fertility.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Expression and Function of the Testis-Predominant Protein LYAR in Mice

Lee

Jin

Choi

et al. 2013

Molecules and Cells

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“…4); thus, it is unlikely that LYAR regulates ribosome biogenesis via increased c-Myc expression or affecting c-Myc function. Recently, functional relationship between the tumor suppressor p53 and Lyar was shown using the knockout mice of these genes (Wang et al 2012). p53 is activated by perturbation of ribosome biogenesis and leads to cell-cycle arrest and apoptosis as reported in animal models of Treacher-Collins syndrome (TCS) that is a congenital disorder of craniofacial development arising from mutations in the TCOF1 gene (Jones et al 2008;Fumagalli & Thomas 2011).…”

Section: Discussionmentioning

confidence: 99%

Human cell growth regulator Ly‐1 antibody reactive homologue accelerates processing of preribosomal RNA

et al. 2014

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Ribosome biogenesis is an essential process for cell growth and proliferation and is enhanced in cancer and embryonic stem cells. Mouse Ly-1 antibody reactive clone product (Lyar) is expressed at very high levels in many tumor, leukemia or embryonic stem cells; is a novel nucleolar protein with zinc-finger DNA-binding motifs and is involved in cell growth regulation. However, cellular function of Lyar remains unexplored. Here, we show that human homologue of Lyar (LYAR) accelerates ribosome biogenesis at the level of processing of preribosomal RNA (pre-rRNA). We show that LYAR is excluded from the nucleolus after actinomycin D treatment and is present in preribosomal fraction of the nuclear extract as well as in the fractions with 40S, 60S and 90S sedimentation coefficients. LYAR is required for processing of 47S/45S, 32S, 30S and 21S pre-rRNAs. In addition, we show that over-expression of LYAR increases cell proliferation without affecting the expression of c-Myc or p53. Combined, these results suggest that some rapidly growing cells enhance ribosome biogenesis by increasing the expression of LYAR.

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“…The sex-specific effect of p53 loss on neural tube closure has been ascribed to differences in X gene dosage [ 70 ]. In addition, the zinc finger protein, Lyar, has been shown to function synergistically with p53 loss in promoting NTDs and death of female embryos [ 71 ].…”

Section: Mechanisms Of Sex Effects In Cancermentioning

confidence: 99%

An integrative view on sex differences in brain tumors

Sun

Plutynski

Ward

et al. 2015

Cell. Mol. Life Sci.

169

120

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Sex differences in human health and disease can range from undetectable to profound. Differences in brain tumor rates and outcome are evident in males and females throughout the world and regardless of age. These observations indicate that fundamental aspects of sex determination can impact the biology of brain tumors. It is likely that optimal personalized approaches to the treatment of male and female brain tumor patients will require recognizing and understanding the ways in which the biology of their tumors can differ. It is our view that sex-specific approaches to brain tumor screening and care will be enhanced by rigorously documenting differences in brain tumor rates and outcomes in males and females, and understanding the developmental and evolutionary origins of sex differences. Here we offer such an integrative perspective on brain tumors. It is our intent to encourage the consideration of sex differences in clinical and basic scientific investigations.

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Mutations in Lyar and p53 are synergistically lethal in female mice

Cited by 15 publications

References 41 publications

Expression and Function of the Testis-Predominant Protein LYAR in Mice

Expression and Function of the Testis-Predominant Protein LYAR in Mice

Human cell growth regulator Ly‐1 antibody reactive homologue accelerates processing of preribosomal RNA

An integrative view on sex differences in brain tumors

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