scholarly journals Usp26 mutation in mice leads to defective spermatogenesis depending on genetic background

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kohei Sakai ◽  
Chizuru Ito ◽  
Mizuki Wakabayashi ◽  
Satoko Kanzaki ◽  
Toshiaki Ito ◽  
...  
Keyword(s):  
Male Infertility ◽  
Genetic Background ◽  
Chiasma Formation ◽  
Mutant Mice ◽  
Reproductive Capacity ◽  
Wild Type ◽  
Human Male ◽  
Subsequent Decrease ◽  
Head Morphology ◽  
Defective Spermatogenesis

Abstract Spermatogenesis is a reproductive system process that produces sperm. Ubiquitin specific peptidase 26 (USP26) is an X chromosome-linked deubiquitinase that is specifically expressed in the testes. It has long been controversial whether USP26 variants are associated with human male infertility. Thus, in the present study, we introduced a mutation into the Usp26 gene in mice and found that Usp26 mutant males backcrossed to a DBA/2 background, but not a C57BL/6 background, were sterile or subfertile and had atrophic testes. These findings indicate that the effects of the Usp26 mutation on male reproductive capacity were influenced by genetic background. Sperm in the cauda epididymis of Usp26 mutant mice backcrossed to a DBA/2 background were decreased in number and showed a malformed head morphology compared to those of wild-type mice. Additionally, histological examinations of the testes revealed that the number of round and elongated spermatids were dramatically reduced in Usp26 mutant mice. The mutant mice exhibited unsynapsed chromosomes in pachynema and defective chiasma formation in diplonema, which presumably resulted in apoptosis of metaphase spermatocytes and subsequent decrease of spermatids. Taken together, these results indicate that the deficiencies in fertility and spermatogenesis caused by mutation of Usp26 were dependent on genetic background.

scholarly journals The links between hypertrophy, reproductive potential and longevity in the Saccharomyces cerevisiae yeast.

2016 ◽  
Vol 63 (2) ◽  
Author(s):  
Mateusz Molon ◽  
Renata Zadrag-Tecza
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Volume ◽  
Genetic Background ◽  
Wild Type Strain ◽  
Reproductive Potential ◽  
Model Organism ◽  
Reproductive Capacity ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Daughter Cells

The yeast Saccharomyces cerevisiae has long been used as a model organism for studying the basic mechanisms of aging. However, the main problem with the use of this unicellular fungus is the unit of "longevity". For all organisms, lifespan is expressed in units of time, while in the case of yeast it is defined by the number of daughter cells produced. Additionally, in yeast the phenotypic effects of mutations often show a clear dependence on the genetic background, suggesting the need for an analysis of strains representing different genetic backgrounds. Our results confirm the data presented in earlier papers that the reproductive potential is strongly associated with an increase in cell volume per generation. An excessive cell volume results in the loss of reproductive capacity. These data clearly support the hypertrophy hypothesis. The time of life of all analysed mutants, with the exception of sch9D, is the same as in the case of the wild-type strain. Interestingly, the 121% increase of the fob1D mutant's reproductive potential compared to the sfp1D mutant does not result in prolongation of the mutant's time of life (total lifespan).

scholarly journals SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility

2019 ◽  
Author(s):  
Samantha L.P. Schilit ◽  
Shreya Menon ◽  
Corinna Friedrich ◽  
Tammy Kammin ◽  
Ellen Wilch ◽  
...  
Keyword(s):  
Male Infertility ◽  
Exome Sequencing ◽  
Synaptonemal Complex ◽  
Budding Yeast ◽  
Reproductive Age ◽  
Severe Oligozoospermia ◽  
Common Cause ◽  
Human Male ◽  
Defective Spermatogenesis

ABSTRACTInfertility is one of the most common disorders for men of reproductive age. To identify novel genetic etiologies, we studied a male with severe oligozoospermia and 46, XY,t(20;22)(q13.3;q11.2). We identified exclusive overexpression of SYCP2 from the der(20) allele that is hypothesized to result from enhancer adoption. Modeling the dysregulation in budding yeast resulted in disruption of the synaptonemal complex, a common cause of defective spermatogenesis in mammals. Exome sequencing of infertile males revealed three novel heterozygous SYCP2 frameshift variants in additional subjects with cryptozoospermia and azoospermia. This study provides the first evidence of SYCP2-mediated male infertility in humans.

scholarly journals Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements

2020 ◽  
Author(s):  
Maik Hintze ◽  
Sebastian Griesing ◽  
Marion Michels ◽  
Birgit Blanck ◽  
Lena Wischhof ◽  
...  
Keyword(s):  
Hair Growth ◽  
Transcriptional Regulators ◽  
Mutant Mice ◽  
Wild Type ◽  
Protein Levels ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Keratinocyte Cell ◽  
Apoptosis Inducing Factor ◽  
Hair Cortex

AbstractWe investigated the contribution of apoptosis-inducing factor (AIF), a key regulator of mitochondrial biogenesis, in supporting hair growth. We report that pelage abnormalities developed during hair follicle (HF) morphogenesis in Harlequin (Hq) mutant mice. Fragility of the hair cortex was associated with decreased expression of genes encoding structural hair proteins, though key transcriptional regulators of HF development were expressed at normal levels. Notably, Aifm1 (R200 del) knockin males and Aifm1(R200 del)/Hq females showed minor hair defects, despite substantially reduced AIF levels. Furthermore, we cloned the integrated ecotropic provirus of the Aifm1Hq allele. We found that its overexpression in wild-type keratinocyte cell lines led to down-regulation of HF-specific Krt84 and Krtap3-3 genes without altering Aifm1 or epidermal Krt5 expression. Together, our findings imply that pelage paucity in Hq mutant mice is mechanistically linked to severe AIF deficiency and is associated with the expression of retroviral elements that might potentially influence the transcriptional regulation of structural hair proteins.

scholarly journals Supplier-origin mouse microbiomes significantly influence locomotor and anxiety-related behavior, body morphology, and metabolism

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Aaron C. Ericsson ◽  
Marcia L. Hart ◽  
Jessica Kwan ◽  
Louise Lanoue ◽  
Lynette R. Bower ◽  
...  
Keyword(s):  
Genetic Background ◽  
Hematological Parameters ◽  
Disease Models ◽  
Wild Type ◽  
Physical And Mental Health ◽  
Model Species ◽  
Fecal Microbiome ◽  
Host Behavior ◽  
Profound Influence ◽  
Models Of Disease

AbstractThe mouse is the most commonly used model species in biomedical research. Just as human physical and mental health are influenced by the commensal gut bacteria, mouse models of disease are influenced by the fecal microbiome (FM). The source of mice represents one of the strongest influences on the FM and can influence the phenotype of disease models. The FM influences behavior in mice leading to the hypothesis that mice of the same genetic background from different vendors, will have different behavioral phenotypes. To test this hypothesis, colonies of CD-1 mice, rederived via embryo transfer into surrogate dams from four different suppliers, were subjected to phenotyping assays assessing behavior and physiological parameters. Significant differences in behavior, growth rate, metabolism, and hematological parameters were observed. Collectively, these findings show the profound influence of supplier-origin FMs on host behavior and physiology in healthy, genetically similar, wild-type mice maintained in identical environments.

scholarly journals Variations in Antioxidant Genes and Male Infertility

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bolan Yu ◽  
Zhaofeng Huang
Keyword(s):  
Male Infertility ◽  
Population Studies ◽  
Sperm Quality ◽  
Synergistic Effects ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Functional Polymorphisms ◽  
Normal Sperm ◽  
Oxide Synthase ◽  
Defective Spermatogenesis

Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathioneS-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.

Lingual deficits in BDNF and NT3 mutant mice leading to gustatory and somatosensory disturbances, respectively

Development ◽  
1997 ◽  
Vol 124 (7) ◽  
pp. 1333-1342 ◽  
Author(s):  
C.A. Nosrat ◽  
J. Blomlof ◽  
W.M. ElShamy ◽  
P. Ernfors ◽  
L. Olson
Keyword(s):  
Taste Buds ◽  
Mutant Mice ◽  
Taste Bud ◽  
Physiological Data ◽  
Clinical Implications ◽  
Wild Type ◽  
Severe Reduction ◽  
Sensory Modalities ◽  
Per Se ◽  
Taste Discrimination

A combination of anatomical, histological and physiological data from wild-type and null-mutated mice have established crucial roles for BDNF and NT3 in gustatory and somatosensory innervation of the tongue, and indeed for proper development of the papillary surface of the tongue. BDNF is expressed in taste buds, NT3 in many surrounding epithelial structures. Absence of BDNF in mice leads to severely malformed taste bud-bearing papillae and severe reduction of taste buds, a loss of proper innervation of remaining taste buds and a loss of taste discrimination although not of the suckling reflex per se. In contrast, absence of NT3 leads to a massive loss of somatosensory innervation of lingual structures. These findings demonstrate distinct roles for BDNF and NT3 in the establishment of the complex innervation apparatus of the tongue with non-overlapping roles for the lingual gustatory and somatosensory systems. The distinction between different sensory modalities, being dependent on either BDNF or NT3 may also have clinical implications.

Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

2021 ◽  
Author(s):  
Haider Z. Naqvi
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Genetic Background ◽  
Germ Line ◽  
Strong Indication ◽  
Wild Type ◽  
C Elegans ◽  
Novel Gene ◽  
Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

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