Karim Nayernia

University of Georgia, Атина, Georgia, United States

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Publications (82)332.75 Total impact

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    ABSTRACT: We have examined the effect of retinoic acid (RA) on differentiation of bone marrow derived CD15(+) , Oct4(+) and CXCR4(+) cells into male germ cells. Bone marrow stem cells (BMSCs) were isolated from the femur of 3-4 week old male C57BL/6 mice. Magnetic-activated cell sorting (MACS) system was used to sort CD15(+) , Oct4(+) and CXCR4(+) cells. RT-PCR was used to follow the expression of pluripotency markers. Sorted CD15(+) , Oct4(+) and CXCR4(+) cells were cultured in an undifferentiated condition on a feeder layer of mitomycin C-inactivated C2C12. The embryoid-like bodies were differentiated into male germ cells by retinoic acid. To identify the expression of male germ specific markers, differentiated cells were analysed by means of reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence staining. RT-PCR and immunofluorescence show that bone marrow derived CD15(+) , Oct4(+) and CXCR4(+) cells express pluripotency markers, Oct4, Nanog, Rex-1, SOX-2 and AP. The purified CD15(+) , Oct4(+) and CXCR4(+) formed structures like embryoid bodies when plated over a feeder layer; these bodies were alkaline phosphatase positive. When cells were induced by RA, bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+) were positive for Mvh, Dazl, Piwil2, Dppa3 and Stra8, that known molecular markers of male germ cells. Thus RA can induce differentiation of mouse bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+) cells into male germ cells in vitro. Negative results for the gene expression analysis of female germ cells markers, GDF9 and ZP3, confirmed this conclusion.
    Cell Biology International 02/2014; · 1.64 Impact Factor
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    ABSTRACT: Piwil2, a member of Ago/Piwi gene family containing Piwi and PAZ domains, has been shown to be ectopically expressed in different cancer cells, especially its remarkable expression in cancer stem cells (CSCs), and is also known to be essential for germ line stem cell self-renewal in various organisms. The hypothesis that CSC may hold the key to the central problem of clinical oncology and tumor relapse leads to more anticancer treatment studies. Due to emerging controversies and extreme difficulties in studying of CSC, like the cells using in vivo models, more attempts have expended to establish different in vitro models. However, the progress was slow owing to the problems associated with establishing proper CSC cultures in vitro. To overcome these difficulties, we prompted to establish a novel stable cell line over-expressing Piwil2 to develop a potential proper in vitro CSC model. In this experimental study, mouse embryonic fibroblasts (MEFs) were isolated and electroporated with a construct containing Piwil2 cDNA under the control of the cytomegalovirus promoter (CMV). Stable transfectants were selected, and the established MEF-Piwil2 cell line was characterized and designated as CSC-like cells using molecular markers. Functional assays, including proliferation, migration, and invasion assays were performed using characterized CSC like cells in serum-free medium. Additionally, MEF-Piwil2 cell density and viability were measured by direct and indirect methods in normoxic and hypoxic conditions. The results of reverse transcriptase-polymerase chain reaction (RT-PCR), western blot, and immunocytochemistry revealed an overexpression for Piwil2 in the transfected Piwil2 cells both in the RNA and protein levels. Furthermore, analysis of the kinetic and stoichiometric parameters demonstrated that the specific growth rate and the yield of lactate per glucose were significantly higher in the MEF-Piwil2 group compared to the MEF cells (ANOVA, p< 0.05). Also, analysis of functional assays including migration and invasion assays demonstrated a significantly higher number of migrated and invaded cells in the MEF-Piwil2 compared to that of the MEF cells (ANOVA, p< 0.05). The MEF-Piwil2 cells tolerated hypoxia mimetic conditions (CoCl2 ) with more than 95% viability. According to the molecular and functional studies, it has been realized that Piwil2 plays a key role(s) in tumor initiation, progression and metastasis. Therefore, Piwil2 can be used not only as a common biomarker for tumor, but also as a target for the development of new anticancer drug. Finally, the main outcome of our study was the establishment of a novel CSC-like in vitro model which is expected to be utilized in understanding the complex roles played by CSC in tumor maintenance, metastasis, therapy resistance or cancer relapse.
    Cell Journal 01/2013; 15(3):250-7. · 0.23 Impact Factor
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    ABSTRACT: Sperm and eggs are essential cells for reproduction and fertility in mammals. Lack of sperm production is one of the leading causes of infertility, a major and growing problem in the developed world affecting 13 to 18% of reproductive-age couples. The birth of the first test tube baby by in vitro fertilization marked an advance in infertility treatment. Later on, several important new techniques called assisted reproductive technologies were developed to help couples who experience infertility. One limiting factor is the requirement of reproductive cells (gametes) for use in in vitro fertilization. For azoospermic men lacking sperm cells, producing gametes in vitro could be a new window to overcome infertility. In the past few years, several reports have been published on generating germ cells from stem cells, one of the epitomes of which was the report on functional in vitro-derived (IVD) germ cells. These mature haploid sperm cells from mouse embryonic stem cells were capable of egg fertilization and producing live offspring. In tandem with previous advancements in germ cell research, development of new technologies based on IVD gametes will change the future of infertility and provide a new basis for the establishment of novel therapeutic approaches to cure more complicated conditions of infertility. In addition, IVD gametogenesis provides an accessible system for studying the specification and differentiation of sperm cells and related processes such as meiosis, morphogenesis, and motility.
    Seminars in Reproductive Medicine 01/2013; 31(1):33-38. · 3.21 Impact Factor
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    ABSTRACT: The evidence of germ cell derivation from embryonic and somatic stem cells provides an in vitro model for the study of germ cell development, the associated epigenetic modification and mammalian gametogenesis. More importantly, in vitro derived gametes also represent a potential strategy for treating infertility. In mammals, male and female gametes, oocyte and sperm, are derived from a specific cell population, primordial germ cells (PGCs), that segregate early in embryogenesis. In the present study we tried to isolate pluripotent SSEA-1+ cells from mice bone marrow using MACS system. The SSEA-1+ cells were directly separated from the suspension of murine mononuclear cells (MMCs) harvested from bone marrow of 2-4 weeks old mice. Flowcytometry assay immediately after sorting and culturing under undifferentiated condition showed 55±7% and 87±4% purity, respectively. RT-PCR analysis after differentiation of SSEA-1+ cells into derivations of three germ layers, revealed the pluripotency properties of isolated cells. The SSEA-1+ cells were induced to differentiate along germ cell lineage by adding bone morphogenic factor-4 (BMP4) to medium. The expression of germ cell markers (PGCs, male and female germ cell lineage) was investigated. It is found that adding exogenous BMP4 into culture medium could differentiate pluripotent SSEA-1+ cells isolated from an adult tissue into gametes precursors, primordial germ cells. Differentiated cells expressed specific molecular markers of primordial germ cells including Oct4, fragilis, Stella, and Mvh. Our results showed that BMP4 is not sufficient to induce SSEA-1+ cells-derived PGCs to develop further into late germ cells in vitro.
    Cell Biology International 09/2012; · 1.64 Impact Factor
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    ABSTRACT: During the last few years, the Islamic republic of Iran has consistently grown in nearly all scientific fields and achieved considerable success in producing science and developing technology. The Iranian government and scientific community have jointly started programs to support the creation of new scientific opportunities and technology platforms for research in the domain of stem cell and tissue engineering. In addition, clinical translation of basic researches in the fields of stem cell and regenerative medicine has been amongst the top priorities. Interestingly, the public sector, media, and authorities are also actively monitoring these attainments. In spite of this nationwide interest, however, there is currently a dearth of analytical information on these accomplishments. To address this issue, here we introduce the key decisions made by the country's policy makers and also review some of the Iranian researchers' publications in this field.
    Stem cell reviews 02/2012; 8(3):629-39. · 5.08 Impact Factor
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    ABSTRACT: Previous studies showed that in the mouse mutant Lis1(GT/GT) gene trap integration in intron 2 of Lis1 gene leads to male infertility in homozygous Lis1(GT/GT) mice. We further analyzed this line and could confirm the suggested downregulation of a testis-specific Lis1 transcript in mutant animals in a quantitative manner. Moreover, we analyzed the gene trap mutation on different genetic backgrounds in incipient congenic animals and could exclude a genetic background effect. To gain further insights into the role and requirement of LIS1 in spermatogenesis, 3 transgenic lines were generated, that overexpress Lis1 under control of the testis-specific promoters hEF-1α, which is exclusively active in spermatogonial cells, PGK2, which is active in pachytene spermatocytes and following stages of spermatogenesis, and Tnp2 which is active in round spermatids and following stages of spermatogenesis, respectively. All 3 transgenic lines remained fertile and testis sections displayed no abnormalities. To overcome the infertility of Lis1(GT/GT) males, these transgenic Lis1-overexpressing animals were mated with Lis1(GT/GT) mice to generate 'rescued' Lis1(GT/GT)/Lis1(Tpos) males. 'Rescued' animals from all transgenic lines remained infertile, thus overexpression of Lis1 in different stages of spermatogenesis could not rescue the infertility phenotype of homozygous gene trap males.
    Cytogenetic and Genome Research 01/2011; 134(4):269-82. · 1.84 Impact Factor
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    ABSTRACT: Cancer stem cell studies may improve understanding of tumor pathophysiology and identify more effective strategies for cancer treatment. In a variety of organisms, Piwil2 has been implicated in multiple roles including stem cell self-renewal, RNA silencing, and translational control. In this study, we documented specific expression of the stem cell protein Piwil2 in breast cancer with predominant expression in breast cancer stem cells. In patients who were evaluated, we determined that 90% of invasive carcinomas and 81% of carcinomas in situ exhibited highest expression of Piwil2. In breast cancer cells, Piwil2 silencing suppressed the expression of signal transducer and activator of transcription 3, a pivotal regulator of Bcl-X(L) and cyclin D1, whose downregulation paralleled a reduction in cell proliferation and survival. Our findings define Piwil2 and its effector signaling pathways as key factors in the proliferation and survival of breast cancer stem cells.
    Cancer Research 06/2010; 70(11):4569-79. · 9.28 Impact Factor
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    ABSTRACT: Spermatogonial stem cells (SSCs) provide the basis for spermatogenesis throughout adult life by undergoing self-renewal and differentiation into sperm. SSC-derived cell lines called multipotent adult germline stem cells (maGSCs) were recently shown to be pluripotent and to have the same potential as embryonic stem cells (ESCs). In a differentiation protocol using retinoic acid (RA) and based on a double selection strategy, we have shown that ESCs are able to undergo meiosis and produce haploid male germ cells in vitro. Using this differentiation protocol we have now succeeded to generate haploid male germ cells from maGSCs in vitro. maGSCs derived from a Stra8-EGFP transgenic mouse line were differentiated into stable spermatogonial stages and further cultured. These cells were transfected with a postmeiotic specific promoter construct Prm1-DsRed to monitor retinoic acid (RA) induced differentiation into haploid male gametes. Our protocol is another approach for the production of pluripotent stem cell derived gametes (PSCDGs) and is an alternative for the investigation of mammalian spermatogenesis, germ line gene modification and epigenetic reprogramming. If reproducible with pluripotent cell lines derived from human SSCs, it could also be used as a therapeutic approach for the treatment of male infertility.
    Differentiation 01/2010; 80(4-5):184-94. · 2.86 Impact Factor
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    ABSTRACT: Multipotent adult germ-line stem cells (maGSCs) represent a new pluripotent cell type that can be derived without genetic manipulation from spermatogonial stem cells (SSCs) present in adult testis. Similarly to induced pluripotent stem cells (iPSCs), they could provide a source of cellular grafts for new transplantation therapies of a broad variety of diseases. To test whether these stem cells can be rejected by the recipients, we have analyzed whether maGSCs and iPSCs can become targets for cytotoxic T lymphocytes (CTL) or whether they are protected, as previously proposed for embryonic stem cells (ESCs). We have observed that maGSCs can be maintained in prolonged culture with or without leukemia inhibitory factor and/or feeder cells and still retain the capacity to form teratomas in immunodeficient recipients. They were, however, rejected in immunocompetent allogeneic recipients, and the immune response controlled teratoma growth. We analyzed the susceptibility of three maGSC lines to CTL in comparison to ESCs, iPSCs, and F9 teratocarcinoma cells. Major histocompatibility complex (MHC) class I molecules were not detectable by flow cytometry on these stem cell lines, apart from low levels on one maGSC line (maGSC Stra8 SSC5). However, using a quantitative real time PCR analysis H2K and B2m transcripts were detected in all pluripotent stem cell lines. All pluripotent stem cell lines were killed in a peptide-dependent manner by activated CTLs derived from T cell receptor transgenic OT-I mice after pulsing of the targets with the SIINFEKL peptide. Pluripotent stem cells, including maGSCs, ESCs, and iPSCs can become targets for CTLs, even if the expression level of MHC class I molecules is below the detection limit of flow cytometry. Thus they are not protected against CTL-mediated cytotoxicity. Therefore, pluripotent cells might be rejected after transplantation by this mechanism if specific antigens are presented and if specific activated CTLs are present. Our results show that the adaptive immune system has in principle the capacity to kill pluripotent and teratoma forming stem cells. This finding might help to develop new strategies to increase the safety of future transplantations of in vitro differentiated cells by exploiting a selective immune response against contaminating undifferentiated cells. This article was reviewed by Bhagirath Singh, Etienne Joly and Lutz Walter.
    Biology Direct 09/2009; 4:31. · 2.72 Impact Factor
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    ABSTRACT: This article, "In Vitro Derivation of Human Sperm from Embryonic Stem Cells," is being retracted from Stem Cells and Development. Further details will follow online, and in a subsequent issue of the Journal.
    Stem cells and development 08/2009; · 4.15 Impact Factor
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    ABSTRACT: The germline of sexually reproducing animals, at some point in development, consists of both proliferating and differentiating cells. For the reproductive strategy of a given species, regulating the timing and number of gametes, and thus controlling the timing of differentiation and the extent of proliferation, is very important for reproductive fitness. Therefore, animals have evolved regulatory mechanisms that tightly control and balance the proliferation-initiation of meiotic development decision. Piwi proteins have been implicated in stem cell self-renewal and germ cell development in a wide variety of organisms. Recently, it was shown that lack of Piwil2 (piwi-like 2, Mili) blocks spermatogenesis at an early phase of meiosis. To reveal the dose-dependent function of Piwil2 in spermatogenesis, transgenic mice overexpressing Piwil2 in premeiotic germ cells were produced and analyzed. Although transgenic mice showed normal spermatogenesis at early puberty ages, germ cell development was impaired at later stages. A decreased number of sperm was observed due to the degeneration of spermatocytes and spermatid arrest. As determined by histological analysis and TUNEL assay for apoptotic cells, Piwil2 (Mili) transgenic mice showed an increase in apoptosis compared to wild-type. These results indicate that pachytene spermatocytes and metaphase cells of most damaged tubules arrest their differentiation program. Our results, together with recent findings, reveal that stem cell protein Piwil2 (Mili) regulates germ cell development during spermatogenesis in a dose-dependent manner. Mol. Reprod. Dev. 2009. (c) 2009 Wiley-Liss, Inc.
    Molecular Reproduction and Development 07/2009; · 2.81 Impact Factor
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    ABSTRACT: Reprogramming of a differentiated cell into a cell capable of giving rise to many different cell types, a pluripotent cell, which in turn could repopulate or repair nonfunctional or damaged tissue, would present beneficial applications in regenerative medicine. It was shown by different groups that germ cells can be reprogrammed to pluripotent stem cells in all diploid stages of development. Specification of germline lineage is one of the most essential events in development, since this process ensures the acquisition, modification, and reservation of the totipotent genome for subsequent generations. We and other groups have shown that adult male germline stem cells, spermatogonial stem cells, can be converted into embryonic stem cell–like cells that can differentiate into the somatic stem cells of three germ layers. Importantly, cultured germ cells demonstrate normal and stable karyotypes as well as normal patterns of genomic imprinting. Transplantation studies have begun in a variety of models in hopes of defining their potential application of pluripotent stem cells derived from germ cells to treat a wide variety of human conditions, including cardiovascular and neurological disorders. This chapter describes general considerations regarding molecular and cellular aspects of reprogramming of germ cells at different developmental stages to stem cells compared with their counterpart, embryonic stem cells. KeywordsGerm cells–Stem cells–Spermatogonial stem cells–Pluripotency–Regenerative medicine
    04/2009: pages 71-81;
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    ABSTRACT: Recently, we reported the successful establishment of multipotent adult germ-line stem cells (maGSCs) from cultured adult mouse spermatogonial stem cells. Similar to embryonic stem cells, maGSCs are able to self-renew and differentiate into derivatives of all three germ layers. These properties make maGSCs a potential cell source for the treatment of neural degenerative diseases. In this study, we describe the generation of maGSC-derived proliferating neural precursor cells using growth factor-mediated neural lineage induction. The neural precursors were positive for nestin and Sox1 and could be continuously expanded. Upon further differentiation, they formed functional neurons and glial cells, as demonstrated by expression of lineage-restricted genes and proteins and by electrophysiological properties. Characterization of maGSC-derived neurons revealed the generation of specific subtypes, including GABAergic, glutamatergic, serotonergic, and dopaminergic neurons. Electrophysiological analysis revealed passive and active membrane properties and postsynaptic currents, indicating their functional maturation. Functional networks formed at later stages of differentiation, as evidenced by synaptic transmission of spontaneous neuronal activity. In conclusion, our data demonstrate that maGSCs may be used as a new stem cell source for basic research and biomedical applications.
    Stem Cell Research 04/2009; 2(2):139-54. · 4.47 Impact Factor
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    ABSTRACT: The successful isolation and cultivation of spermatogonial stem cells (SSCs) as well as induction of SSCs into pluripotent stem cells will allow us to study their biological characteristics and their applications in therapeutic approaches. Here we provide step-by-step procedures on the basis of previous work in our laboratory for: the isolation of testicular cells from adolescent mice by a modified enzymatic procedure; the enrichment of undifferentiated spermatogonia by laminin selection or genetic selection using Stra8-EGFP (enhanced green fluorescent protein) transgenic mice; the cultivation and conversion of undifferentiated spermatogonia into embryonic stem-like cells, so-called multipotent adult germline stem cells (maGSCs); and characterization of these cells. Normally, it will take about 16 weeks to obtain stable maGSC lines starting from the isolation of testicular cells.
    Nature Protocol 02/2009; 4(2):143-54. · 8.36 Impact Factor
  • Mary Herbert, Karim Nayernia, Chay Keogh
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    ABSTRACT: With the potential to develop into any cell type in the body, stem cells promise new therapeutic possibilities for the treatment of tissues damaged by age-related degeneration, injury or disease.
    Imaging & Microscopy 01/2009; 11(4):29-31.
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    ABSTRACT: The derivation of autologous pluripotent cells has become a central goal in translational stem cell research. Although somatic cell nuclear transfer and transcription factor-based reprogramming enable the generation of pluripotent cells from adult tissue, both methodologies depend on complex epigenetic alterations. Recent data suggest that the adult germ line may represent an alternative and natural source of pluripotent stem cells. Multipotent adult germ line stem cells (maGSCs) with properties similar to those of embryonic stem cells have been derived from mouse spermatogonial stem cells. These cells exhibit extensive self-renewal, expression of pluripotency markers, and differentiation into derivatives of all three germ layers. Here we report the derivation of multipotent neural and glial precursors as well as adherently proliferating neural stem cells from maGSCs. Characterization of maGSC-derived neurons revealed segregation into GABAergic, glutamatergic, serotonergic, and tyrosine hydroxylase-positive phenotypes. On a functional level, maGSC-derived neurons generate spontaneously active functional networks, which use both glutamatergic and GABAergic synaptic transmission and engage in synchronized oscillatory activity. maGSC-derived oligodendrocytes undergo full maturation and ensheathe host axons in myelin-deficient tissue. Our data suggest that neural stem and precursor cells derived from maGSCs could provide a versatile and potentially autologous source of functional neurons and glia.
    Stem Cells 09/2008; 26(9):2434-43. · 7.70 Impact Factor
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    ABSTRACT: Spermatogonial stem cells (SSCs) isolated from the adult mouse testis and cultured have been shown to respond to culture conditions and become pluripotent, so called multipotent adult germline stem cells (maGSCs). microRNAs (miRNAs) belonging to the 290 and 302 miRNA clusters have been previously classified as embryonic stem cell (ESC) specific. Here, we show that these miRNAs generally characterize pluripotent cells. They are expressed not only in ESCs but also in maGSCs as well as in the F9 embryonic carcinoma cell (ECC) line. In addition, we tested the time-dependent influence of different factors that promote loss of pluripotency on levels of these miRNAs in all three pluripotent cell types. Despite the differences regarding time and extent of differentiation observed between ESCs and maGSCs, expression profiles of both miRNA families showed similarities between these two cell types, suggesting similar underlying mechanisms in maintenance of pluripotency and differentiation. Our results indicate that the 290-miRNA family is connected with Oct-4 and maintenance of the pluripotent state. In contrast, members of the 302-miRNA family are induced during first stages of in vitro differentiation in all cell types tested. Therefore, detection of miRNAs of miR-302 family in pluripotent cells can be attributed to the proportion of spontaneously differentiating cells in cultures of pluripotent cells. These results are consistent with ESC-like nature of maGSCs and their potential as an alternative source of pluripotent cells from non-embryonic tissues.
    Molecular Human Reproduction 09/2008; 14(9):521-9. · 4.54 Impact Factor
  • Karim Nayernia
    Cell Research 07/2008; · 10.53 Impact Factor
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    ABSTRACT: Hereditary haemorrhagic telangiectasia (HHT), associated with arteriovenous malformations, is a genetic disease of the vascular system with a frequency of approx. 1:10,000. Genetic diagnosis serves to identify individuals at risk of developing the disease and is a useful tool for genetic counselling purposes. Here we report on a child presenting severe arteriovenous malformations leading to heart failure. Her mother and grandmother present fewer symptoms of hereditary haemorrhagic telangiectasia. In this study we identify the cause of HHT in the family. Clinical examination, PCR, DNA sequencing, quantitative PCR, Southern blot, xray, ultrasound, cardiac catheterisation and angiocardiography. Initially the sequence variant in c.392C>T in the endoglin gene was detected in the grandmother, but not in other affected family members. Further analyses revealed a deletion of exon 1 of endoglin, segregating with the phenotype. This report points out the need for careful evaluation of molecular genetic findings, particularly in diseases with highly variable phenotype.
    Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 07/2008; 138(29-30):432-6. · 1.82 Impact Factor
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    ABSTRACT: Human HNRNPGT, encoding the protein hnRNP G-T, is one of several autosomal retrogenes derived from RBMX. It has been suggested that HNRNPGT functionally replaces the sex-linked RBMX and RBMY genes during male meiosis. We show here that during normal mouse germ cell development, hnRNP G-T protein is strongly expressed during and after meiosis when proteins expressed from Rbmx or Rbmx-like genes are absent. Amongst these Rbmx-like genes, DNA sequence analyses indicate that two other mouse autosomal Rbmx-derived retrogenes have evolved recently in rodents and one already shows signs of degenerating into a non-expressed pseudogene. In contrast, orthologues of Hnrnpgt are present in all four major groups of placental mammals. The sequence of Hnrnpgt is under considerable positive selection suggesting it performs an important germ cell function in eutherians. To test this, we inactivated Hnrnpgt in ES cells and studied its function during spermatogenesis in chimaeric mice. Although germ cells heterozygous for this targeted allele could produce sperm, they did not contribute to the next generation. Chimaeric mice with a high level of mutant germ cells were infertile with low sperm counts and a high frequency of degenerate seminiferous tubules and abnormal sperm. Chimaeras made from a 1:1 mix of targeted and wild-type ES cell clones transmitted wild-type germ cells only. Our data show that haploinsufficiency of Hnrnpgt results in abnormal sperm production in the mouse. Genetic defects resulting in reduced levels of HNRNPGT could, therefore, be a cause of male infertility in humans.
    Human Molecular Genetics 07/2008; 17(18):2803-18. · 7.69 Impact Factor

Publication Stats

3k Citations
332.75 Total Impact Points

Institutions

  • 2013
    • University of Georgia
      Атина, Georgia, United States
  • 2012
    • GENEOCELL
      Brossard, Quebec, Canada
  • 1994–2011
    • Universitätsmedizin Göttingen
      • • Department of Human Genetics
      • • Heart Center Göttingen
      • • Department of Cardiology and Pneumology
      Göttingen, Lower Saxony, Germany
  • 2007–2010
    • Newcastle University
      • • Northern Institute for Cancer Research
      • • North East England Stem Cell Institute
      Newcastle upon Tyne, ENG, United Kingdom
  • 1996–2009
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany
  • 2003–2006
    • Institute of Human Genetics
      Amadavad, Gujarāt, India
  • 2002
    • University of Massachusetts Boston
      • Department of Biology
      Boston, Massachusetts, United States