Targeted disruption of the spermatid-specific gene Spata31 causes male infertility

2015 ◽  
Vol 82 (6) ◽  
pp. 432-440 ◽  
Author(s):  
Yuan-Yi Wu ◽  
Yong Yang ◽  
Yong-De Xu ◽  
Hua-Liang Yu
Keyword(s):  
Male Infertility ◽  
Specific Gene ◽  
Targeted Disruption

scholarly journals Targeted disruption of retinoic acid receptor alpha (RAR alpha) and RAR gamma results in receptor-specific alterations in retinoic acid-mediated differentiation and retinoic acid metabolism.

1995 ◽  
Vol 15 (2) ◽  
pp. 843-851 ◽  
Author(s):  
J F Boylan ◽  
T Lufkin ◽  
C C Achkar ◽  
R Taneja ◽  
P Chambon ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Specific Gene ◽  
Cell Type ◽  
Targeted Disruption ◽  
F9 Cells ◽  
Retinoid Receptors ◽  
Alpha Gene ◽  
Polar Derivatives ◽  
Crabp Ii

F9 embryonic teratocarcinoma stem cells differentiate into an epithelial cell type called extraembryonic endoderm when treated with retinoic acid (RA), a derivative of retinol (vitamin A). This differentiation is presumably mediated through the actions of retinoid receptors, the RARs and RXRs. To delineate the functions of each of the different retinoid receptors in this model system, we have generated F9 cell lines in which both copies of either the RAR alpha gene or the RAR gamma gene are disrupted by homologous recombination. The absence of RAR alpha is associated with a reduction in the RA-induced expression of both the CRABP-II and Hoxb-1 (formerly 2.9) genes. The absence of RAR gamma is associated with a loss of the RA-inducible expression of the Hoxa-1 (formerly Hox-1.6), Hoxa-3 (formerly Hox-1.5), laminin B1, collagen IV (alpha 1), GATA-4, and BMP-2 genes. Furthermore, the loss of RAR gamma is associated with a reduction in the metabolism of all-trans-RA to more polar derivatives, while the loss of RAR alpha is associated with an increase in metabolism of RA relative to wild-type F9 cells. Thus, each of these RARs exhibits some specificity with respect to the regulation of differentiation-specific gene expression. These results provide an explanation for the expression of multiple RAR types within one cell type and suggest that each RAR has specific functions.

The abundant retinal protein of the Chlamydomonas eye is not the photoreceptor for phototaxis and photophobic responses

2001 ◽  
Vol 114 (21) ◽  
pp. 3857-3863
Author(s):  
Markus Fuhrmann ◽  
Alke Stahlberg ◽  
Elena Govorunova ◽  
Simone Rank ◽  
Peter Hegemann
Keyword(s):  
Green Alga ◽  
Transcriptional Gene Silencing ◽  
Specific Gene ◽  
Related Protein ◽  
Wild Type ◽  
Targeted Disruption ◽  
Retinal Protein ◽  
Post Transcriptional Gene Silencing ◽  
Unicellular Green Alga ◽  
Efficient Reduction

The chlamyopsin gene (cop) encodes the most abundant eyespot protein in the unicellular green alga Chlamydomonas reinhardtii. This opsin-related protein (COP) binds retinal and was thought to be the photoreceptor controlling photomovement responses via a set of photoreceptor currents. Unfortunately, opsin-deficient mutants are not available and targeted disruption of non-selectable nuclear genes is not yet possible in any green alga. Here we show that intron-containing gene fragments directly linked to their intron-less antisense counterpart provide efficient post-transcriptional gene silencing (PTGS) in C. reinhardtii, thus allowing an efficient reduction of a specific gene product in a green alga. In opsin-deprived transformants, flash-induced photoreceptor currents (PC) are left unchanged. Moreover, photophobic responses as studied by motion analysis and phototaxis tested in a light-scattering assay were indistinguishable from the responses of untransformed wild-type cells. We conclude that phototaxis and photophobic responses in C. reinhardtii are triggered by an as yet unidentified rhodopsin species.

scholarly journals The role of the testis-specific gene hTAF7L in the aetiology of male infertility

2006 ◽  
Vol 12 (4) ◽  
pp. 263-267 ◽  
Author(s):  
K. Stouffs ◽  
A. Willems ◽  
W. Lissens ◽  
H. Tournaye ◽  
A. Van Steirteghem ◽  
...  
Keyword(s):  
Male Infertility ◽  
Specific Gene

scholarly journals Targeted Disruption of Tyrosylprotein Sulfotransferase-2, an Enzyme That Catalyzes Post-translational Protein TyrosineO-Sulfation, Causes Male Infertility

2006 ◽  
Vol 281 (14) ◽  
pp. 9423-9431 ◽  
Author(s):  
Atefeh Borghei ◽  
Ying-Bin Ouyang ◽  
Andrew D. Westmuckett ◽  
Matthew R. Marcello ◽  
Carlisle P. Landel ◽  
...  
Keyword(s):  
Male Infertility ◽  
Targeted Disruption

scholarly journals Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male mice†

2020 ◽  
Vol 103 (2) ◽  
pp. 244-253
Author(s):  
Kaori Nozawa ◽  
Qian Zhang ◽  
Haruhiko Miyata ◽  
Darius J Devlin ◽  
Zhifeng Yu ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Male Infertility ◽  
Sperm Motility ◽  
Sperm Head ◽  
Specific Gene ◽  
Cell Organelles ◽  
Single Pass ◽  
Human Male ◽  
Transmission Electron ◽  
Golgi Network

Abstract Globozoospermia (sperm with an abnormally round head shape) and asthenozoospermia (defective sperm motility) are known causes of male infertility in human patients. Despite many studies, the molecular details of the globozoospermia etiology are still poorly understood. Serine-rich single-pass membrane protein 1 (Ssmem1) is a conserved testis-specific gene in mammals. In this study, we generated Ssmem1 knockout (KO) mice using the CRISPR/Cas9 system, demonstrated that Ssmem1 is essential for male fertility in mice, and found that SSMEM1 protein is expressed during spermatogenesis but not in mature sperm. The sterility of the Ssmem1 KO (null) mice is associated with globozoospermia and loss of sperm motility. To decipher the mechanism causing the phenotype, we analyzed testes with transmission electron microscopy and discovered that Ssmem1-disrupted spermatids have abnormal localization of Golgi at steps eight and nine of spermatid development. Immunofluorescence analysis with anti-Golgin-97 to label the trans-Golgi network, also showed delayed movement of the Golgi to the spermatid posterior region, which causes failure of sperm head shaping, disorganization of the cell organelles, and entrapped tails in the cytoplasmic droplet. In summary, SSMEM1 is crucial for intracellular Golgi movement to ensure proper spatiotemporal formation of the sperm head that is required for fertilization. These studies and the pathway in which SSMEM1 functions have implications for human male infertility and identifying potential targets for nonhormonal contraception.

scholarly journals 255.Dnmt3L: a coordinator of epigenetic modifications during spermatogenesis

2004 ◽  
Vol 16 (9) ◽  
pp. 255
Author(s):  
K. E. Webster ◽  
M. K. O'Bryan ◽  
U. Aapola ◽  
P. E. Crewther ◽  
R. Lyle ◽  
...  
Keyword(s):  
Epigenetic Modifications ◽  
Histone Deacetylation ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Imprinted Genes ◽  
Targeted Disruption ◽  
Biallelic Expression ◽  
Homologous Chromosomes ◽  
Progressive Degeneration ◽  
Chromosome Alignment

Spermatogenesis is a process with unique epigenetic requirements. The differentiation from diploid spermatogonia to haploid spermatozoa requires regulation of genomic imprint establishment, stage specific gene expression, meiotic division, and the histone-protamine transition. The methyltransferase regulator, Dnmt3L, is expressed during gametogenesis and is necessary for establishment of maternal methylation imprints in the oocyte. Targeted disruption of Dnmt3L does not appear to affect oogenesis, as mature oocytes are generated, however resultant heterozygous progeny die mid gestation due to biallelic expression of imprinted genes. Dnmt3L–/– males however show spermatogenic arrest. We found that this arrest occurs during prophase I of meiosis, with spermatocytes lost by both apoptosis and germ cell sloughing. A progressive degeneration ensues, resulting in a Sertoli cell phenotype. Electron microscopy of meiotic spermatocytes revealed that homologous chromosomes fail to align and form synaptonemal complexes. Furthermore, Dnmt3L–/– spermatocytes show abnormal methylation on paternally imprinted genes and abnormal global retention of histone acetylation, implicating Dnmt3L in histone deacetylase recruitment. Thus, during spermatogenesis, Dnmt3L is crucial for two distinct epigenetic modifications; imprint establishment and global histone deacetylation prior to homologous chromosome alignment. The latter defect is likely to affect the alignment of homologous chromosomes and trigger the pachytene checkpoint leading to spermatocyte death. Since Dnmt3L has no DNA methlytransferase or HDAC activity itself, we propose that Dnmt3L is essential for the coordination of epigenetic layers, at least during spermatogenesis.

scholarly journals Male Infertility Caused by a de Novo Partial Deletion of the DAZ Cluster on the Y Chromosome1

2000 ◽  
Vol 85 (11) ◽  
pp. 4069-4073
Author(s):  
Enrico Moro ◽  
Alberto Ferlin ◽  
Pauline Hsiao Yen ◽  
Paolo Guanciali Franchi ◽  
Giandomenico Palka ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
Point Mutations ◽  
De Novo Mutation ◽  
Specific Gene ◽  
Partial Deletion ◽  
Severe Oligozoospermia ◽  
First Case ◽  
Factor C ◽  
Spermatogenic Failure

Deletions in distal Yq interval 6 represent the cause of 10–15% of idiopathic severe male infertility and map to a region defined AZFc (azoospermia factor c). The testis-specific gene DAZ is considered a major AZFc candidate, and its deletion has been associated with a severe disruption in spermatogenesis. However, DAZ is actually a multicopy gene family consisting of seven clustered copies spanning about 1 megabase. Only deletions removing the entire DAZ gene cluster together with other genes have been reported in infertile males. Because no case of spermatogenic failure has been traced to intragenic deletions, point mutations, or even deletions not involving all the DAZ copies, the definitive proof for a requirement of DAZ for spermatogenesis is still debatable. Here we report the first case of a partial deletion of the DAZ cluster removing all but one of the copies. This deletion is present in a patient affected with severe oligozoospermia who had a testicular phenotype characterized by a great quantitative reduction of germ cells (severe hypospermatogenesis). The absence of this deletion in the fertile brother of the patient suggests that this de novo mutation indeed caused the spermatogenic failure.

scholarly journals Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice

2008 ◽  
Vol 17 (21) ◽  
pp. 3368-3379 ◽  
Author(s):  
Si-Tse Jiang ◽  
Yuan-Yow Chiou ◽  
Ellian Wang ◽  
Hsiu-Kuan Lin ◽  
Sue-Ping Lee ◽  
...  
Keyword(s):  
Male Infertility ◽  
Targeted Disruption

Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11

Development ◽  
1994 ◽  
Vol 120 (8) ◽  
pp. 2187-2198 ◽  
Author(s):  
A.P. Davis ◽  
M.R. Capecchi
Keyword(s):  
Male Infertility ◽  
Gene Targeting ◽  
Vertebral Column ◽  
Hox Genes ◽  
Incomplete Penetrance ◽  
Appendicular Skeleton ◽  
Long Bones ◽  
Paralogous Gene ◽  
Targeted Disruption ◽  
Limb Deformities

Using gene targeting, we have created mice with a disruption in the homeobox-containing gene hoxd-11. Homozygous mutants are viable and the only outwardly apparent abnormality is male infertility. Skeletons of mutant mice show a homeotic transformation that repatterns the sacrum such that each vertebra adopts the structure of the next most anterior vertebra. Defects are also seen in the bones of the limb, including regional malformations at the distal end of the forelimb affecting the length and structure of phalanges and metacarpals, inappropriate fusions between wrist bones, and defects at the most distal end in the long bones of the radius and ulna. The phenotypes show both incomplete penetrance and variable expressivity. In contrast to the defects observed in the vertebral column, the phenotypes in the appendicular skeleton do not resemble homeotic transformations, but rather regional malformations in the shapes, length and segmentation of bones. Our results are discussed in the context of two other recent gene targeting studies involving the paralogous gene hoxa-11 and another member of the Hox D locus, hoxd-13. The position of these limb deformities reflects the temporal and structural colinearity of the Hox genes, such that inactivation of 3′ genes has a more proximal phenotypic boundary (affecting both the zeugopod and autopod of the limb) than that of the more 5′ genes (affecting only the autopod). Taken together, these observations suggest an important role for Hox genes in controlling localized growth of those cells that contribute to forming the appendicular skeleton.

Targeted disruption of the bradyzoite-specific gene BAG1 does not prevent tissue cyst formation in Toxoplasma gondii

1998 ◽  
Vol 92 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Wolfgang Bohne ◽  
Christopher A Hunter ◽  
Michael W White ◽  
David J.P Ferguson ◽  
Uwe Gross ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cyst Formation ◽  
Tissue Cyst ◽  
Specific Gene ◽  
Targeted Disruption
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