scholarly journals Mice Lacking the UBC4-testis Gene Have a Delay in Postnatal Testis Development but Normal Spermatogenesis and Fertility

2005 ◽  
Vol 25 (15) ◽  
pp. 6346-6354 ◽  
Author(s):  
Nathalie Bedard ◽  
Pascal Hingamp ◽  
Zhiyu Pang ◽  
Andrew Karaplis ◽  
Carlos Morales ◽  
...  
Keyword(s):  
Germ Cells ◽  
Abdominal Cavity ◽  
Testis Weight ◽  
Wild Type ◽  
Early Maturation ◽  
Ubiquitinated Proteins ◽  
Adult Mice ◽  
Normal Spermatogenesis ◽  
The Many ◽  
Ubiquitin Conjugating Enzymes

ABSTRACT Activation of ubiquitination occurs during spermatogenesis and is dependent on the induction of isoforms of the UBC4 family of ubiquitin-conjugating enzymes. The UBC4-testis isoform is testis specific, is induced in round spermatids, and demonstrates biochemical functions distinct from a ubiquitously expressed isoform UBC4-1. To explore further the function of UBC4-testis, mice bearing inactivation of this gene were produced. Homozygous (−/−) mice showed normal body growth and fertility. Although testis weight and morphology were normal in testes from adult mice, examination of young mice during the first wave of spermatogenesis revealed that testes were ∼10% smaller in weight at 40 and 45 days of age but had become normal at 65 days of age. Overall protein content, levels of ubiquitinated proteins, and ubiquitin-conjugating activity did not differ between wild-type and homozygous (−/−) mice. Spermatid number, as well as the motility of spermatozoa isolated from the epididymis, was also normal in homozygous (−/−) mice. To determine whether the germ cells lacking UBC4-testis might be more sensitive to stress, testes from wild-type and knockout mice were exposed to heat stress by implantation in the abdominal cavity. Testes from both strains of mice showed similar rates of degeneration in response to heat. The lack of an obvious phenotype did not appear to be due to induction of other UBC4 isoforms, as shown by two-dimensional gel immunoblotting. Our data indicate that UBC4-testis plays a role in early maturation of the testis and suggest that the many UBC4 isoforms have mixed redundant and specific functions.

Restoration of spermatogenesis by high levels of testosterone in hypophysectomized rats after long-term regression

1987 ◽  
Vol 116 (4) ◽  
pp. 433-444 ◽  
Author(s):  
H. F. S. Huang ◽  
G. R. Marshall ◽  
R. Rosenberg ◽  
E. Nieschlag
Keyword(s):  
Germ Cell ◽  
Normal Control ◽  
Germ Cells ◽  
Cell Number ◽  
Testis Weight ◽  
The Status ◽  
Hypophysectomized Rats ◽  
Normal Spermatogenesis ◽  
Successive Generations

Abstract. In order to correlate the levels of intratesticular testosterone and the status of spermatogenesis, the present study examined the spermatogenic responses of mature chronically hypophysectomized (HPX) rats to different regimens of testosterone (T) replacement, i.e. implantation of a 2 × 5 or 6 × 5 cm long testosterone capsule (TC), or injection of 25 mg or 100 mg of testosterone enanthate (TE) every 4 days for 90 days. These regimens restored the testicular testosterone of the HPX rats to 25–96% of that measured in normal control rats. The testis weight of untreated HPX rats was below 30% of the normal control values. It was restored to 60–80% of control values in the TC implanted rats and to 50% in those receiving TE injection. Complete spermatogenesis of HPX rats was restored in those receiving TC implants and 100 mg TE injections. It was incomplete in those given 25 mg TE injections. Quantitative evaluation of germ cells revealed that spermatogonial populations of HPX rats were restored to 70 and 50% of the normal levels in rats receiving TC implants and TE injection, respectively. Differentiation of these cells resulted in the population of preleptotene spermatocytes to the same extent as those observed in spermatogonia. The yield of spermatids in both TC- and TE-treated HPX rats was below 50% of normal controls. Ratios between two successive generations of germ cells in stage VII epithelium revealed both dosage and regimen effects upon the yield of meiotic cells and spermatids. These results suggest that both T concentration and the mode of T availability to the testis may be important for specific steps of germ cell development in different stages of the cycle of the seminiferous epithelium. The results of the present study demonstrate that as little as 25% of normal testicular T concentration is sufficient to support all stages of spermatogenesis. Failure to restore a normal germ cell number even in the presence of a normal testicular T concentration suggests the need of other factors for quantitative spermatogenesis. Furthermore, despite a higher testicular T concentration achieved by TE injections, the restoration of spermatogenesis was less pronounced by this regimen. This finding suggests that the consistency of testicular T may also be important for normal spermatogenesis.

scholarly journals Loss of TSLC1 Causes Male Infertility Due to a Defect at the Spermatid Stage of Spermatogenesis

2006 ◽  
Vol 26 (9) ◽  
pp. 3595-3609 ◽  
Author(s):  
Louise van der Weyden ◽  
Mark J. Arends ◽  
Oriane E. Chausiaux ◽  
Peter J. Ellis ◽  
Ulrike C. Lange ◽  
...  
Keyword(s):  
Expression Profiling ◽  
Embryonic Stem ◽  
Null Mutation ◽  
Spermatogenic Cells ◽  
Wild Type ◽  
Stem Cell Technology ◽  
Adult Mice ◽  
Normal Spermatogenesis ◽  
Low Levels ◽  
Normal Differentiation

ABSTRACT Tumor suppressor of lung cancer 1 (TSLC1), also known as SgIGSF, IGSF4, and SynCAM, is strongly expressed in spermatogenic cells undergoing the early and late phases of spermatogenesis (spermatogonia to zygotene spermatocytes and elongating spermatids to spermiation). Using embryonic stem cell technology to generate a null mutation of Tslc1 in mice, we found that Tslc1 null male mice were infertile. Tslc1 null adult testes showed that spermatogenesis had arrested at the spermatid stage, with degenerating and apoptotic spermatids sloughing off into the lumen. In adult mice, Tslc1 null round spermatids showed evidence of normal differentiation (an acrosomal cap and F-actin polarization indistinguishable from that of wild-type spermatids); however, the surviving spermatozoa were immature, malformed, found at very low levels in the epididymis, and rarely motile. Analysis of the first wave of spermatogenesis in Tslc1 null mice showed a delay in maturation by day 22 and degeneration of round spermatids by day 28. Expression profiling of the testes revealed that Tslc1 null mice showed increases in the expression levels of genes involved in apoptosis, adhesion, and the cytoskeleton. Taken together, these data show that Tslc1 is essential for normal spermatogenesis in mice.

scholarly journals Down-regulation of collagen XI during late post-natal corneal development is followed by up-regulation after injury

2021 ◽  
Author(s):  
Mei Sun ◽  
Devon Cogswell ◽  
Sheila Adams ◽  
Yasmin Ayoubi ◽  
Ambuj Kumar ◽  
...  
Keyword(s):  
Spatial Localization ◽  
Corneal Tissue ◽  
Wild Type ◽  
Temporal Expression ◽  
Knockout Mouse Model ◽  
Early Maturation ◽  
Adult Mice ◽  
Corneal Development ◽  
Temporal And Spatial ◽  
Fibril Diameter

Collagen XI plays a role in nucleating collagen fibrils and in controlling fibril diameter. The aim of this research is to elucidate the role that collagen XI plays in corneal fibrillogenesis during development and following injury. The temporal and spatial expression of collagen XI was evaluated in C57BL/6 wild type (WT) mice. For wound healing studies in adult mice, stromal injuries were created using techniques that avoid caustic chemicals. The temporal expression and spatial localization of collagen XI was studied following injury in a Col11a1 inducible knockout mouse model. We found that collagen XI expression occurs during early maturation and is upregulated after stromal injury in areas of regeneration and remodeling. Abnormal fibrillogenesis with new fibrils of heterogenous size and shape occurs after injury in a decreased collagen XI matrix. In conclusion, we found that collagen XI is expressed in the stroma during development and following injury in adults. Collagen XI is a regulator of collagen fibrillogenesis in regenerating corneal tissue.

Reduced urea flux across the blood-testis barrier and early maturation in the male reproductive system in UT-B-null mice

2007 ◽  
Vol 293 (1) ◽  
pp. C305-C312 ◽  
Author(s):  
Lirong Guo ◽  
Dan Zhao ◽  
Yuanlin Song ◽  
Yan Meng ◽  
Huashan Zhao ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Male Reproductive System ◽  
Testis Weight ◽  
Wild Type ◽  
Early Puberty ◽  
Early Maturation ◽  
Androgen Binding

A urea-selective urine-concentrating defect was found in transgenic mice deficient in urea transporter (UT)-B. To determine the role of facilitated urea transport in extrarenal organs expressing UT-B, we studied the kinetics of [14C]urea distribution in UT-B-null mice versus wild-type mice. After renal blood flow was disrupted, [14C]urea distribution was selectively reduced in testis in UT-B-null mice. Under basal conditions, total testis urea content was 335.4 ± 43.8 μg in UT-B-null mice versus 196.3 ± 18.2 μg in wild-type mice ( P < 0.01). Testis weight in UT-B-null mice (6.6 ± 0.8 mg/g body wt) was significantly greater than in wild-type mice (4.2 ± 0.8 mg/g body wt). Elongated spermatids were observed earlier in UT-B-null mice compared with wild type mice on day 24 versus day 32, respectively. First breeding ages in UT-B knockout males (48 ± 3 days) were also significantly earlier than that in wild-type males (56 ± 2 days). In competing mating tests with wild-type males and UT-B-null males, all pups carried UT-B-targeted genes, which indicates that all pups were produced from breeding of UT-B-null males. Experiments of the expression of follicle-stimulating hormone receptor (FSHR) and androgen binding protein (ABP) indicated that the development of Sertoli cells was also earlier in UT-B-null mice than that in wild-type mice. These results suggest that UT-B plays an important role in eliminating urea produced by Sertoli cells and that UT-B deletion causes both urea accumulation in the testis and early maturation of the male reproductive system. The UT-B knockout mouse may be a useful experimental model to define the molecular mechanisms of early puberty.

scholarly journals 278.Bioactive activin and its effects on murine testis development

2004 ◽  
Vol 16 (9) ◽  
pp. 278
Author(s):  
S. H. S. Mendis ◽  
S. Meachem ◽  
C. Brown ◽  
K. L. Loveland
Keyword(s):  
Body Weight ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Transforming Growth Factor ◽  
Activin A ◽  
Testicular Development ◽  
Testis Weight ◽  
Wild Type ◽  
Coding Sequence

Activin is a member of the TGF β (Transforming Growth Factor β) superfamily of ligands which influence many aspects of male germ cell development. Formed by the linkage of two common β subunits, activin A (a βA βA dimer) has been reported to (1) cause apoptosis of primodial germ cells, (2) inhibit the cellular transition of gonocytes into undifferentiated spermatogonia, and (3) enhance FSH-mediated stimulation of Sertoli cell proliferation in the newborn rat testis. Although closely related, activin βA and activin βB (a βB:βB dimer) differ in that activin βB is less bioactive. In this study we examined the role of activin during the first wave of spermatogenesis using knockout (Inhba–/–) and transgenic (InhbaBK/BK; two copies of the βB subunit gene coding sequence replace the βA coding sequence) mouse models with reduced levels of bioactive activin. Absolute gonocyte and Sertoli cell numbers were significantly elevated in the absence of activin A in newborn Inhba–/– testes compared to wild type, as determined by optical disector analysis. As the Inhba–/– mice die at birth, we next studied the BK/BK mice to examine postnatal effects of reduced activin bioactivity. Surprisingly, both body weight and testis weight were lower in the BK/BK compared to wild type mice at Day 7 and 14, but testis growth in proportion to body weight was significantly reduced between 7 and 14 days. At 2 weeks of age, the BK/BK animal displays a significant reduction in Sertoli cells and specific subpopulations of germ cells, the latter of which was evident only in heterozygote animals. Examination of these two models has identified that lower levels of bioactive activin affect Sertoli cells and germ cells at different stages of testicular development. Our ongoing studies involving RNA analyses of various candidate target genes will facilitate a greater understanding of the molecular basis for these observations.

scholarly journals Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia

2004 ◽  
Vol 166 (4) ◽  
pp. 559-570 ◽  
Author(s):  
Shin-ichiro Kitajiri ◽  
Kanehisa Fukumoto ◽  
Masaki Hata ◽  
Hiroyuki Sasaki ◽  
Tatsuya Katsuno ◽  
...  
Keyword(s):  
Hair Cells ◽  
Plasma Membranes ◽  
Wild Type ◽  
Cross Link ◽  
Erm Proteins ◽  
Hearing Ability ◽  
Adult Mice ◽  
Progressive Degeneration ◽  
Sensory Hair Cells

Ezrin/radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wild-type mice, radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that radixin-deficient (Rdx−/−) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset (∼2 wk), in the cochlea and vestibule of Rdx−/− mice, stereocilia developed normally in which ezrin was concentrated. As these Rdx−/− mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx−/− mice. Thus, we concluded that radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once developed. In Rdx−/− mice, ezrin appeared to compensate for radixin deficiency in terms of the development of cochlear stereocilia and the development/maintenance of vestibular stereocilia. These findings indicated the existence of complicate functional redundancy in situ among ERM proteins.

Impaired wound healing in embryonic and adult mice lacking vimentin

2000 ◽  
Vol 113 (13) ◽  
pp. 2455-2462 ◽  
Author(s):  
B. Eckes ◽  
E. Colucci-Guyon ◽  
H. Smola ◽  
S. Nodder ◽  
C. Babinet ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wild Type ◽  
Impaired Wound Healing ◽  
Wound Site ◽  
Adult Mice ◽  
Tractional Forces ◽  
Filament Network ◽  
Vimentin Intermediate Filament

It is generally assumed that the vimentin intermediate filament network present in most mesenchymally-derived cells is in part responsible for the strength and integrity of these cells, and necessary for any tissue movements that require the generation of significant tractional forces. Surprisingly, we have shown that transgenic KO mice deficient for vimentin are apparently able to undergo embryonic development absolutely normally and go onto develop into adulthood and breed without showing any obvious phenotype. However, fibroblasts derived from these mice are mechanically weak and severely disabled in their capacity to migrate and to contract a 3-D collagen network. To assess whether these functions are necessary for more challenging tissue movements such as those driving in vivo tissue repair processes, we have analysed wound healing ability in wild-type versus vimentin-deficient embryos and adult mice. Wounds in vimentin-deficient adult animals showed delayed migration of fibroblasts into the wound site and subsequently retarded contraction that correlated with a delayed appearance of myofibroblasts at the wound site. Wounds made to vimentin-deficient embryos also failed to heal during the 24 hour culture period it takes for wild-type embryos to fully heal an equivalent wound. By DiI marking the wound mesenchyme and following its fate during the healing process we showed that this impaired healing is almost entirely due to a failure of mesenchymal contraction at the embryonic wound site. These observations reveal an in vivo phenotype for the vimentin-deficient mouse, and challenge the dogma that key morphogenetic events occurring during development require generation of significant tractional forces by mesenchymal cells.

scholarly journals NBR1 directly promotes the formation of p62 – ubiquitin condensates via its PB1 and UBA domains

2020 ◽  
Author(s):  
Adriana Savova ◽  
Julia Romanov ◽  
Sascha Martens
Keyword(s):  
Phase Separation ◽  
Wild Type ◽  
Selective Autophagy ◽  
Ubiquitinated Proteins ◽  
Cargo Receptor ◽  
Condensate Formation ◽  
Uba Domain ◽  
Reconstituted System ◽  
Pb1 Domain

SummarySelective autophagy removes harmful intracellular structures such as ubiquitinated, aggregated proteins ensuring cellular homeostasis. This is achieved by the encapsulation of this cargo material within autophagosomes. The cargo receptor p62/SQSTM1 mediates the phase separation of ubiquitinated proteins into condensates, which subsequently become targets for the autophagy machinery. NBR1, another cargo receptor, is a crucial regulator of condensate formation. The mechanisms of the interplay between p62 and NBR1 are not well understood. Employing a fully reconstituted system we show that two domains of NBR1, the PB1 domain which binds to p62 and the UBA domain which binds to ubiquitin, are required to promote p62-ubiquitin condensate formation. In cells, acute depletion of endogenous NBR1 reduces formation of p62 condensates, a phenotype that can be rescued by re-expression of wild-type NBR1, but not PB1 or UBA domain mutants. Our results provide mechanistic insights into the role of NBR1 in selective autophagy.

INHERITANCE OF RADIATION-INDUCED SPINAL CURVATURES IN THE GUPPY LEBISTES RETICULATUS

1969 ◽  
Vol 11 (4) ◽  
pp. 937-947 ◽  
Author(s):  
Johannes Horst Schröder
Keyword(s):  
Germ Cells ◽  
Vertebral Column ◽  
Segregation Ratio ◽  
X Rays ◽  
Wild Type ◽  
Spinal Curvatures ◽  
Recessive Mutations ◽  
Quantitative Characters ◽  
Radiation Induced ◽  
Lebistes Reticulatus

Hereditary changes in the shape of the vertebral column in Lebistes reticulatus appeared after ancestral irradiation of immature germ cells with 500 or 1000 R of X-rays. Although the mutant to wild-type ratios in the F2 generation after outcrossing fitted a digenic and a trigenic segregation ratio, respectively, the quantitative characters in question are assumed to be caused by recessive mutations of polygenes which are highly mutable.

Sex determination in the germ line of Drosophila melanogaster: activation of the gene Sex-lethal

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 813-816 ◽  
Author(s):  
B. Granadino ◽  
P. Santamaria ◽  
L. Sanchez
Keyword(s):  
Drosophila Melanogaster ◽  
Germ Cells ◽  
Germ Line ◽  
Wild Type ◽  
Female Development ◽  
Pole Cell ◽  
Somatic Tissues ◽  
Wild Type Female ◽  
Sex Lethal ◽  
Pole Cell Transplantation

The germ line exhibits sexual dimorphism as do the somatic tissues. Cells with the 2X;2A chromosome constitution will follow the oogenic pathway and X;2A cells will develop into sperm. In both somatic and germ-line tissues, the sexual pathway chosen by the cells depends on the gene Sex-lethal (Sxl), whose function is continuously needed for female development. In the soma, the sex of the cells is autonomously determined by the X:A signal while, in the germ line, the sex is determined by cell autonomous (the X:A signal) and somatic inductive signals. Three X-linked genes have been identified, scute (sc), sisterless-a (sis-a) and runt (run), that determine the initial functional state of Sxl in the soma. Using pole cell transplantation, we have tested whether these genes are also needed to activate Sxl in the germ line. We found that germ cells simultaneously heterozygous for sc, sis-a, run and a deficiency for Sxl transplanted into wild-type female hosts develop into functional oocytes. We conclude that the genes sc, sis-a and run needed to activate Sxl in the soma seem not to be required to activate this gene in the germ line; therefore, the X:A signal would be made up by different genes in somatic and germ-line tissues. The Sxlf7M1/Sxlfc females do not have developed ovaries. We have shown that germ cells of this genotype transplanted into wild-type female hosts produce functional oocytes. We conclude that the somatic component of the gonads in Sxlf7M1/Sxlfc females is affected, and consequently germ cells do not develop.(ABSTRACT TRUNCATED AT 250 WORDS)

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