282 IDENTIFICATION OF SRY AND STEROIDOGENIC FACTOR-1 (SF1) GENES IN CANINE XY MALE-TO-FEMALE SEX DEVELOPMENTAL DISORDER

2011 ◽  
Vol 23 (1) ◽  
pp. 239
Author(s):  
G. H. Jang ◽  
Y. H. Jeong ◽  
I. S. Hwang ◽  
Y. W. Jeong ◽  
S. H. Hyun ◽  
...  
Keyword(s):  
Sex Determination ◽  
Cultured Cells ◽  
Mammalian Species ◽  
Gene Mutations ◽  
Sex Reversal ◽  
Normal Donor ◽  
Sry Gene ◽  
German Shepherd ◽  
Steroidogenic Factor 1 ◽  
Wide Range

Cloning by the process of somatic cell nuclear transfer (SCNT) has been achieved in a variety of mammalian species and has many promising applications. In this process, however, due to reasons beyond current scientific understanding, many results contrary to expectation have also been produced. For instance, abnormal sex development such as demasculinization has been observed in 1 of 6 healthy German shepherd offspring produced with SCNT (1 normal donor (not cloned), 5 cloned but normally developed progenies, 1 cloned sex reversed progeny, and 1 recloned sex reversed progeny from 1 cloned sex reversed progeny). Sex-determining region Y (SRY) is one of the most basic and crucial genes that initiate male sex determination in many mammals. Steroidogenic factor-1 (SF1, NR5A1), which is closely related to SRY, also regulates several genes involved in sex determination. Numerous studies have reported that reduced or deleted SRY gene expression as well as SF1 gene mutations can produced XY sex reversal. To verify the hypothetical association between phenotypic disorder of sex determination and genetic modification by SCNT, we extracted genomic DNA from tissues of normal progeny (not cloned), primary cultured cells of cloned but normally developed progeny, cloned sex reversed progeny, and recloned sex reversed progeny at the age of 1 year and carried out PCR with produced primers based on available SRY and SF1 gene information (SRY gene from AF107021 in GenBank; SF1 gene from ENSCAFG00000023086 in Ensembl). The cloned PCR products were subcloned into T-vector for sequence analysis, which showed no mutation in genetic sequences of SRY and SF1. Taken together, in our case of abnormal sex determination, there was no apparent association between phenotypic sex determination disorder and SRY/SF1 gene mutation. Other sex reversal and related mutation studies have pointed to a wide range of signal networks that include Sox9 and so forth. Further studies should be focused on these other genes in the signal network.

scholarly journals Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs

2020 ◽  
Vol 118 (2) ◽  
pp. e2008743118
Author(s):  
Stefanie Kurtz ◽  
Andrea Lucas-Hahn ◽  
Brigitte Schlegelberger ◽  
Gudrun Göhring ◽  
Heiner Niemann ◽  
...  
Keyword(s):  
Sex Determination ◽  
Mutational Analysis ◽  
Mammalian Species ◽  
Digital Pcr ◽  
Sex Reversal ◽  
Large Animal Model ◽  
Pcr Analysis ◽  
Large Animal ◽  
Sry Gene ◽  
Sex Development

The sex-determining region on the Y chromosome (SRY) is thought to be the central genetic element of male sex development in mammals. Pathogenic modifications within the SRY gene are associated with a male-to-female sex reversal syndrome in humans and other mammalian species, including rabbits and mice. However, the underlying mechanisms are largely unknown. To understand the biological function of the SRY gene, a site-directed mutational analysis is required to investigate associated phenotypic changes at the molecular, cellular, and morphological level. Here, we successfully generated a knockout of the porcine SRY gene by microinjection of two CRISPR-Cas ribonucleoproteins, targeting the centrally located “high mobility group” (HMG), followed by a frameshift mutation of the downstream SRY sequence. This resulted in the development of genetically male (XY) pigs with complete external and internal female genitalia, which, however, were significantly smaller than in 9-mo-old age-matched control females. Quantitative digital PCR analysis revealed a duplication of the SRY locus in Landrace pigs similar to the known palindromic duplication in Duroc breeds. Our study demonstrates the central role of the HMG domain in the SRY gene in male porcine sex determination. This proof-of-principle study could assist in solving the problem of sex preference in agriculture to improve animal welfare. Moreover, it establishes a large animal model that is more comparable to humans with regard to genetics, physiology, and anatomy, which is pivotal for longitudinal studies to unravel mammalian sex determination and relevant for the development of new interventions for human sex development disorders.

Inherited Missense Mutation Occurring in Arginine76 of the SRY Gene Does Not Account for Familial 46, XY Sex Reversal

2020 ◽  
Vol 105 (5) ◽  
pp. 1355-1365
Author(s):  
Nan Wang ◽  
Wenjiao Zhu ◽  
Bing Han ◽  
Hao Wang ◽  
Hui Zhu ◽  
...  
Keyword(s):  
Sex Determination ◽  
Missense Mutation ◽  
Transcriptional Activity ◽  
Nuclear Translocation ◽  
Sex Reversal ◽  
Chromosome 17 ◽  
Sry Gene ◽  
Single Nucleotide ◽  
Xy Sex Reversal ◽  
Sox9 Gene

Abstract Background SRY (sex determining region of Y) is one of the important genes involved in the process of human sex determination. The disturbed sex determination caused by an SRY mutation accounts for 10% to 15% of cases with 46, XY sex reversal. Recently, 3 distal enhancers were identified upstream of the SOX9 gene. Objectives The purpose of this study was to investigate the molecular etiology of 46, XY sex reversal in 3 familial patients and a sporadic patient. Design Next-generation sequencing was used to reveal the genotype and inherited pattern. Copy number variations and single nucleotide polymorphism haplotyping were analyzed to observe the alteration of enhancers of SOX9. Transcriptional activity of SRY mutation were assessed by a dual luciferase reporting system, and nuclear translocation was observed by confocal microscopy. Results Two novel SRY gene mutations, p.Arg76Leu and p.Glu89flx15, were identified. In the pedigree with multiple patients, p.Arg76Leu mutation in SRY and p.Gly212Ser mutation in NR5A1 were identified in the proband. The heterozygous deletion far upstream of the SOX9 gene in chromosome 17 was identified in the 3 patients in this family, containing the distal enhancer eSR-A of SOX9 but not eSR-B and eALDI. The frameshift mutation p.Glu89flx15 was revealed to inhibit the transcriptional activity of the target gene, whereas the missense mutation p.Arg76Leu barely showed an effect. Conclusion In contrast to sporadic cases, inherited single nucleotide variations of SRY are not the main cause of the severe phenotype of 46, XY sex reversal, and the enhancers of SOX9 should be investigated carefully in such patients.

scholarly journals The knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs

2019 ◽  
Author(s):  
Stefanie Kurtz ◽  
Andrea Lucas-Hahn ◽  
Brigitte Schlegelberger ◽  
Gudrun Göhring ◽  
Heiner Niemann ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Mammalian Species ◽  
High Mobility ◽  
Digital Pcr ◽  
Sex Reversal ◽  
Female Genitalia ◽  
Large Animal Model ◽  
Large Animal ◽  
Sry Gene ◽  
Male Sex

1AbstractThe sex-determining region on the Y chromosome (SRY) is thought to be the central genetic element of male sex development. Mutations within the SRY gene are associated with a male-to-female sex reversal syndrome in humans and other mammalian species such as mice and rabbits. However, the underlying mechanisms are largely unknown. To understand the biological function of the SRY gene, a site-directed mutational analysis is required to investigate associated phenotypic changes at the molecular, cellular and morphological level. In our study, we successfully generated a knockout of the porcine SRY gene by microinjection of two clustered regularly interspaced short palindromic repeats (CRISPR) – associated protein - 9 nuclease (Cas9) ribonucleoprotein (RNP) complexes targeting the centrally located “high mobility group” (HMG) domain of the SRY gene. Mutations within this region resulted in the development of complete external and internal female genitalia in genetically male pigs. The internal female genitalia including uteri, ovaries, and oviducts, revealed substantial size differences in 9-months old SRY-knockout pigs compared to age-matched female wild type controls. In contrast, a deletion within the 5’ flanking region of the HMG domain was not associated with sex reversal. Results of this study demonstrates for the first time the central role of the HMG domain of the SRY gene in male sex determination in pigs. Moreover, quantitative analysis by digital PCR revealed evidence for a duplication of the porcine SRY locus. Our results pave the way towards the generation of boars exclusively producing phenotypically female offspring to avoid surgical castration without anesthesia in piglets. Moreover, the study establishes a large animal model that is much more similar to humans in regard of physiology and anatomy and pivotal for longitudinal studies.

scholarly journals Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination

1999 ◽  
Vol 87 (1-2) ◽  
pp. 175-180 ◽  
Author(s):  
N.A. Hanley ◽  
S.G. Ball ◽  
M. Clement-Jones ◽  
D.M. Hagan ◽  
T. Strachan ◽  
...  
Keyword(s):  
Sex Determination ◽  
Gonadal Development ◽  
Wilms Tumour ◽  
Steroidogenic Factor 1 ◽  
Early Human

scholarly journals Sex Ratios in a Warming World: Thermal Effects on Sex-Biased Survival, Sex Determination, and Sex Reversal

2021 ◽  
Vol 112 (2) ◽  
pp. 155-164
Author(s):  
Suzanne Edmands
Keyword(s):  
High Temperature ◽  
Sex Ratio ◽  
Sex Determination ◽  
Heat Tolerance ◽  
Sex Ratios ◽  
Sex Reversal ◽  
Survival Sex ◽  
Ratio Distortion ◽  
Warming World ◽  
Sex Ratio Distortion

Abstract Rising global temperatures threaten to disrupt population sex ratios, which can in turn cause mate shortages, reduce population growth and adaptive potential, and increase extinction risk, particularly when ratios are male biased. Sex ratio distortion can then have cascading effects across other species and even ecosystems. Our understanding of the problem is limited by how often studies measure temperature effects in both sexes. To address this, the current review surveyed 194 published studies of heat tolerance, finding that the majority did not even mention the sex of the individuals used, with <10% reporting results for males and females separately. Although the data are incomplete, this review assessed phylogenetic patterns of thermally induced sex ratio bias for 3 different mechanisms: sex-biased heat tolerance, temperature-dependent sex determination (TSD), and temperature-induced sex reversal. For sex-biased heat tolerance, documented examples span a large taxonomic range including arthropods, chordates, protists, and plants. Here, superior heat tolerance is more common in females than males, but the direction of tolerance appears to be phylogenetically fluid, perhaps due to the large number of contributing factors. For TSD, well-documented examples are limited to reptiles, where high temperature usually favors females, and fishes, where high temperature consistently favors males. For temperature-induced sex reversal, unambiguous cases are again limited to vertebrates, and high temperature usually favors males in fishes and amphibians, with mixed effects in reptiles. There is urgent need for further work on the full taxonomic extent of temperature-induced sex ratio distortion, including joint effects of the multiple contributing mechanisms.

A PCR assay for sex determination of yak (Bos grunniens) meat by amplification of the male-specific SRY gene

Food Control ◽  
2010 ◽  
Vol 21 (5) ◽  
pp. 726-731 ◽  
Author(s):  
W.L. Bai ◽  
R.H. Yin ◽  
S.J. Zhao ◽  
C. Li ◽  
Z.J. Ma ◽  
...  
Keyword(s):  
Sex Determination ◽  
Sry Gene ◽  
Pcr Assay ◽  
Bos Grunniens ◽  
Male Specific

The molecular biology of SRY and its role in sex determination in mammals

1995 ◽  
Vol 7 (4) ◽  
pp. 713 ◽  
Author(s):  
P Koopman
Keyword(s):  
Molecular Biology ◽  
Transgenic Mice ◽  
Sex Determination ◽  
Gene Product ◽  
Mode Of Action ◽  
Recent Progress ◽  
Sry Gene ◽  
Testis Development ◽  
Direct Demonstration

SRY is the gene that initiates the genetic cascade leading to testis development in mammals. Since its discovery in 1990 and the direct demonstration of its male-determining role in transgenic mice, attention has turned to understanding the biochemical mode of action of the SRY gene product, and to the identification of other genes in the sex-determining pathway. Recent progress in these efforts is summarized in this review.

Roles of Anti-Müllerian hormone (Amh) and its duplicates in sex determination and germ cell proliferation of Nile tilapia

Genetics ◽  
2021 ◽  
Author(s):  
Xingyong Liu ◽  
Shengfei Dai ◽  
Jiahong Wu ◽  
Xueyan Wei ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sex Determination ◽  
Germ Cell ◽  
Y Chromosome ◽  
X Chromosome ◽  
Nile Tilapia ◽  
Critical Period ◽  
Sex Reversal ◽  
Homozygous Mutation ◽  
Germ Cell Proliferation

Abstract Duplicates of amh are crucial for fish sex determination and differentiation. In Nile tilapia, unlike in other teleosts, amh is located on X chromosome. The Y chromosome amh (amh△-y) is mutated with 5 bp insertion and 233 bp deletion in the coding sequence, and tandem duplicate of amh on Y chromosome (amhy) has been identified as the sex determiner. However, the expression of amh, amh△-y and amhy, their roles in germ cell proliferation and the molecular mechanism of how amhy determines sex is still unclear. In this study, expression and functions of each duplicate were analyzed. Sex reversal occurred only when amhy was mutated as revealed by single, double and triple mutation of the three duplicates in XY fish. Homozygous mutation of amhy in YY fish also resulted in sex reversal. Earlier and higher expression of amhy/Amhy was observed in XY gonads compared with amh/Amh during sex determination. Amhy could inhibit the transcription of cyp19a1a through Amhr2/Smads signaling. Loss of cyp19a1a rescued the sex reversal phenotype in XY fish with amhy mutation. Interestingly, mutation of both amh and amhy in XY fish or homozygous mutation of amhy in YY fish resulted in infertile females with significantly increased germ cell proliferation. Taken together, these results indicated that up-regulation of amhy during the critical period of sex determination makes it the sex-determining gene, and it functions through repressing cyp19a1a expression via Amhr2/Smads signaling pathway. Amh retained its function in controlling germ cell proliferation as reported in other teleosts, while amh△-y was nonfunctionalized.

Ecological interactions in the transmission of the leishmaniases

1988 ◽  
Vol 321 (1207) ◽  
pp. 389-404 ◽  
Keyword(s):  
Human Disease ◽  
Mammalian Species ◽  
Epidemiological Studies ◽  
Ecological Interactions ◽  
Environmental Barriers ◽  
Human Host ◽  
Phlebotomine Sandfly ◽  
Ecological Changes ◽  
Wide Range ◽  
Epidemiological Pattern

Epidemiological studies on the leishmaniases are disclosing a multiplicity of Leishmania species infecting a wide range of wild mammalian hosts, from marsupials to monkeys. In the primitive, silvatic habitat these parasites are transmitted by an equally wide variety of phlebotomine sandfly species (Diptera: Psychodidae: Phlebotominae). Transmission is not haphazard, however, and available evidence points to the existence of environmental barriers that normally limit the different Leishmania species to specific sandfly vectors, transmitting to certain mammalian species, within distinct ecotopes. In this situation, humans may become infected by a variety of leishmanial parasites when intruding into the different enzootics, if the sandfly vectors are anthropophilic. Many are not, however, and their parasites rarely, if ever, make contact with the human host. Natural or man-made ecological changes may result in modification of the epidemiological pattern of leishmaniasis, leading to either a reduction or an increase in the human disease.

scholarly journals Heat shock induces protein tyrosine phosphorylation in cultured cells.

1989 ◽  
Vol 108 (6) ◽  
pp. 2029-2035 ◽  
Author(s):  
P A Maher ◽  
E B Pasquale
Keyword(s):  
Heat Shock ◽  
Tyrosine Phosphorylation ◽  
Cultured Cells ◽  
Protein Tyrosine Phosphorylation ◽  
Animal Cells ◽  
Protein Tyrosine ◽  
Rous Sarcoma ◽  
Wide Range ◽  
Sarcoma Virus ◽  
Molecular Masses

We examined the effect of heat shock on protein tyrosine phosphorylation in cultured animal cells using antiphosphotyrosine antibodies in immunoblotting and immunofluorescence microscopy experiments. Heat shock significantly elevated the level of phosphotyrosine in proteins in most of the cultured cells examined, including fibroblasts, epithelial cells, nerve cells, and muscle cells, but not in Rous sarcoma virus-transformed fibroblasts. The increase in protein tyrosine phosphorylation induced by heat shock occurred in proteins with a wide range of molecular masses and was dependent on the temperature and duration of the heat shock.

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