EP0536213A1 - Gen, dass das geschlecht entscheidet - Google Patents

Gen, dass das geschlecht entscheidet

Info

Publication number
EP0536213A1
EP0536213A1 EP91911788A EP91911788A EP0536213A1 EP 0536213 A1 EP0536213 A1 EP 0536213A1 EP 91911788 A EP91911788 A EP 91911788A EP 91911788 A EP91911788 A EP 91911788A EP 0536213 A1 EP0536213 A1 EP 0536213A1
Authority
EP
European Patent Office
Prior art keywords
fragment
sry
nucleic acid
sex
gene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP91911788A
Other languages
English (en)
French (fr)
Inventor
Peter Neville Goodfellow
Robin Medical Research Council Lovell-Badge
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cancer Research Horizons Ltd
Original Assignee
Imperial Cancer Research Technology Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB909014446A external-priority patent/GB9014446D0/en
Priority claimed from GB909015488A external-priority patent/GB9015488D0/en
Priority claimed from GB919110085A external-priority patent/GB9110085D0/en
Application filed by Imperial Cancer Research Technology Ltd filed Critical Imperial Cancer Research Technology Ltd
Publication of EP0536213A1 publication Critical patent/EP0536213A1/de
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6879—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for sex determination
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/02—Animal zootechnically ameliorated
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the present invention relates to proteins, polypeptides, nucleic acid fragments, antibodies and related products and to their use in medicine and agriculture, for instance in diagnosis and therapy. More particularly the invention relates to a gene which controls the sex of the embryos of eutherian (placental) mammals and to associated products and their use in ascertaining the sex of cells, embryos and tissues and controlling the sex of the progeny of
  • ZFX a homologue of ZFY. is present on the eutherian X chromosome and escapes
  • Fig. 9. is a diagram of the probe pY53.3 (2.1 kb) subclone.
  • characteristic residue or residues, and/or the fragments will be hybridisable with a Y-chromosome specific sequence associated with the TDF-gene preferably under conditions which substantially prevent hybridisation with any
  • Oligonucleotides containing the mt-box or a part thereof according to the present invention may contain codons specifying one or more of the characteristic amino acid residues discussed above together with neighbouring
  • Antibodies against such proteins and fragments and polypeptides as well as fragments of such antibodies including chemically derived and recombinant fragments of such antibodies, and cells, such as eukaryotic cells, for instance hybridomas and prokaryotic recombinant cells, capable of expressing and, preferably, secreting antibodies or fragments thereof against such proteins or fragments, also form part of the present invention.
  • the nucleic acids of the invention may be obtained by conventional means such as by recovery from organisms using PCR technology or hybridisation probes, by de novo
  • Antibodies may be obtained by immunisation of a suitable host animal and recovery of the antibodies, by culture of antibody-producing cells obtained from suitably immunised host animals or by in vitro stimulation of B-cells with a suitable mt-protein, fragment or polypeptide or mt-mimetope, protein, fragment or polypeptide and culture of the cells. Such cells may be immortalised as necessary for instance by fusion with myeloma cells. Antibody fragments may be obtained by well known chemical and biotechnological methods.
  • eutherian mammal such as a bovine.
  • the thus-identified sequence can then be used to generate primers for PCR which in turn can be used to ascertain the sex of an individual or of cells, tissues, embryos or sperm of the bovine or other mammal. This will permit experiments to ascertain sex to be conducted and controlled sex breeding of the bovine or other mammal as described below.
  • constructs may be used to obtain animals homozygous for one or the other.
  • pY53.3 detected Y- specific fragments (+). All of the probes except pYH8 hybridised to sequences in the XX males. pY4.1B which was positive with the XX males and the probe pYH8 which was negative.
  • the third Y-specific probe, pYRO.4 is derived from sequences lying between pY4-1B and pYH8, and appears to define the break points in the XX males.
  • Fig. 14 shows a comparison of the mouse and human Y-linked nucleotide sequences over 471-bp, in which the degree of homology is 62%.
  • the library was plated using DL652, a bacterial strain that stabilises end to end repeats to overcome problems in cloning the mouse Y
  • Sry-specific oligonucleotide primers (5' - 3') CTGTGTAAGATCTTCAATC and GTGGTGAGAGGCACAAGT and included Hprt primers as a control for the quality and quantity of RNA in each sample.
  • the upper panel shows an ethidium bromide-stained agarose gel with 148 bp PCR products corresponding to Sry transcripts in adult testis and, less intensely, genital ridge (GR) of 11.5 d.p.c. male embryos. The band was absent from adult male liver and 11.5 d.p.c. female genital ridge samples.
  • Sry primers were derived from a single exon and are
  • the conserved protein domain in Sry is homologous to known DNA-binding proteins and, by analogy, the Sry protein could be a nuclear protein that binds DNA and acts as a
  • testis determining gene will play a central role even in those species which do not use a XX/XY chromosome-based system for sex determination.
  • testis determining gene will be a target for experiments to ascertain the sex of cells, tissues, embryos, foetuses, sperm and individuals and to control the sex ratio of the progeny of breeding animals.
  • SRY (or Sry in mice) in the process of testis determination. It satisfies all predictions that can be made concerning the location of the testis determining gene on the Y chromosome.
  • the gene maps to the smallest region of the human and mouse Y chromosomes known to be male determining, and is conserved on the Y chromosome of all other eutherian mammals tested.
  • the gene encodes a putative DNA binding protein, consistent with a regulatory role.
  • Sry also shows a pattern of expression in the mouse entirely consistent with a role in testis determination, being expressed for a short period just prior to overt testis differentiation, specifically in somatic cells of the genital ridge.
  • SRY or Sry containing fragments were isolated from cosmid, phage or plasmid clones by digestion with appropriate restriction enzymes and then purified from other fragments and vector sequences by agarose gel electrophoresis.
  • the isolated DNA fragments were cleaned either by "gene clean” according to manufacturers instructions, or by phenol extraction and by passing down a sephadex G50 column, or an elutip, followed by ethanol precipitation.
  • testis cords Sex reversal of transgenic mouse embryos Fertilised eggs were microinjected with Sry gene sequences, transferred to pseudopregnant recipients, and a proportion of the resulting embryos were analysed at 14 days post transfer, rather than allowing them all to develop to term.
  • the first visible sign of testis development from the genital ridge is the formation of testis cords at about 12.4 dpc in the mouse. This is due to the differentiation of Sertoli cells and their alignment into the epithelial structures surrounding the germ cells [Jost, A. & Marge, S. Phil. Trans. R. Soc. Lond.. 322. 55-61 (1988)].
  • Cord formation confers a characteristic striped appearance to the developing testis, distinguishing it from the fetal ovary. Other morphological changes characteristic of the testis are its rapid growth and prominent vasculature.
  • kb The conserved Sry/SRY open reading frame is indicated by a shaded box. The direction of the open reading frame is shown above the two clones. The position of the human pseudoautosomal boundary is indicated by an arrow, the pseudoautosomal region being to the right of this point.
  • the positions of oligonucleotide primers used for PCR analysis are indicated by triangles.
  • m33.13 has a testis weight of 17mg (in the range expected for an XX Sxr' male), as opposed to 76 mg for an XY littermate.
  • the testes were processed for histology and sections revealed the presence of tubules, with clearly defined and apparently normal populations of Leydig cells, peritubular myoid cells and Sertoli cells, but a complete absence of cells undergoing spermatogensis (Fig. 25c).
  • mice A further two XX transgenics, m32.10 and m33.2, showed an external female phenotype, yet both carried multiple copies of Sry. These mice have produced offspring indicating that they have functional reproductive tract and ovaries. These animals provide further evidence, along with the transgenic XX female fetuses described above, that f741 does not always cause sex reversal. While it is

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Animal Husbandry (AREA)
  • Microbiology (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Chemistry (AREA)
  • Plant Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
EP91911788A 1990-06-28 1991-06-28 Gen, dass das geschlecht entscheidet Withdrawn EP0536213A1 (de)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB9014446 1990-06-28
GB909014446A GB9014446D0 (en) 1990-06-28 1990-06-28 Gene
GB9015488 1990-07-13
GB909015488A GB9015488D0 (en) 1990-07-13 1990-07-13 Gene
GB919110085A GB9110085D0 (en) 1991-05-09 1991-05-09 Sex determining gene
GB9110085 1991-05-09

Publications (1)

Publication Number Publication Date
EP0536213A1 true EP0536213A1 (de) 1993-04-14

Family

ID=27265163

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91911788A Withdrawn EP0536213A1 (de) 1990-06-28 1991-06-28 Gen, dass das geschlecht entscheidet

Country Status (5)

Country Link
EP (1) EP0536213A1 (de)
JP (1) JPH05507850A (de)
AU (1) AU670229B2 (de)
CA (1) CA2085102A1 (de)
WO (1) WO1992000375A1 (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU4225593A (en) * 1992-05-01 1993-11-29 Genzyme Corporation Method for identifying transgenic preimplantation embryos
WO1998046747A2 (en) * 1997-04-11 1998-10-22 Whitehead Institute For Biomedical Research Genes in the non-recombining region of the y chromosome
DE69834527T2 (de) 1997-07-01 2007-05-10 VLP Watertown Limited Partnership, Watertown Verfahren zur Geschlechtsbestimmung von Säuger-Nachkommenschaft
GB9926161D0 (en) * 1999-11-04 2000-01-12 Pig Improvement Company Uk Lim Methods
EP2141049A1 (de) 2008-07-04 2010-01-06 Arno Martin Sauer Halterungsvorrichtung für ein Kennzeichenschild
CN101792802B (zh) * 2010-02-10 2012-06-27 四川大学华西医院 SRY特异性TaqMan探针引物对与实时荧光SRY基因检测试剂盒
KR102386101B1 (ko) * 2014-06-26 2022-04-14 리제너론 파마슈티칼스 인코포레이티드 표적화된 유전자 변형을 위한 방법 및 그 조성물, 및 사용 방법
CN112481308B (zh) * 2019-09-11 2023-04-25 中国科学院分子植物科学卓越创新中心 新型性别决定基因hakai、其调控作用及其应用
CN114958982A (zh) * 2021-02-25 2022-08-30 杭州易文赛生物技术有限公司 用于荧光定量pcr检测痕量人源sry基因的核酸试剂和试剂盒以及方法
CN113122539B (zh) * 2021-04-15 2023-12-05 石河子大学 一种驴Zfy基因的RNA干扰片段、表达载体及其应用
CN115961058B (zh) * 2022-12-29 2024-10-22 石河子大学 检测zfy基因的巢式pcr特异性引物、试剂盒及母猪早期妊娠诊断方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE87979T1 (de) * 1986-08-12 1993-04-15 Univ Australian Geschlechtsbestimmung bei wiederkaeuern unter verwendung y-chromosomenspezifischer polynukleotide.
WO1989002440A2 (en) * 1987-09-21 1989-03-23 Whitehead Institute For Biomedical Research Y-specific dna hybridization probes and uses therefor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9200375A1 *

Also Published As

Publication number Publication date
AU670229B2 (en) 1996-07-11
AU8093191A (en) 1992-01-23
JPH05507850A (ja) 1993-11-11
CA2085102A1 (en) 1991-12-29
WO1992000375A1 (en) 1992-01-09

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