Cloning of V region fragments from mouse liver DNA and localization of repetitive DNA sequences in the vicinity of immunoglobulin gene segments

Steinmetz, Michael; Höchtl, Josef; Schnell, Hannelore; Gebhard, Wolfgang; Zachau, Hans G.

doi:10.1093/nar/8.8.1721

Cited by 29 publications

(11 citation statements)

References 18 publications

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“…The V gene segment that has been rearranged to form the 14 kb EcoRI fragment (Ti) was found on a 3.5 kb EcoRI fragment in liver DNA which has been cloned and characterized (L6 in ref. 19). No hybridization in Southern blotting experiments (not shown) was found between L6 and the nick-translated T3 subclone (Fig.…”

Section: Resultsmentioning

confidence: 90%

A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments

Steinmetz¹,

Altenburger²,

Zachau³

1980

Nucl Acids Res

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A 5.3 kb EcoRI fragment (T3, abbreviations in ref.2) has been cloned from DNA of a kappa light chain producing mouse myeloma. The fragment hybridizes to the 5' flanking sequences of the J1 gene segment but not to C gene sequences of kappa light chain DNA. Restriction nuclease mapping and partial nucleotide sequencing showed that the fragment consists of sequences from the 5' side of the Jl and from the 3' side of a V gene segment, which apparently had been linked in a genomic rearrangement process. These rearranged flanking sequences are not the flanking sequences of the V and J gene segments which had been joined to form the two kappa light chain genes of the myeloma. Fragments with the hybridization properties of T3 have been found also in two other kappa and one lambda chain producing myelomas. The linking of flanking sequences in the myeloma genome is discussed with respect to the mechanism of recombination between V and J gene segments. INTRODUCTIONRearrangement of immunoglobulin light chain gene segments results in the joining of V (variable) and J (joining) gene segments (3,4). Four mechanisms have been proposed for the V-J recombination (5). 1) The copy-insertion model proposes that a V gene segment is duplicated and inserted upstream of a J gene segment.2) The excision-insertion model assumes that the V gene segment itself is excised and then integrated. 3) According to the inversion model a DNA segment is inverted which results in the joining of a V gene segment to a J gene segment in the correct orientation. 4) The deletion model proposes that the DNA segment separating V and J gene segments in germline DNA is deleted in the course of the V-J joining.In sequencing studies with cloned V and J gene fragments a characteristic heptanucleotide sequence was found adjacent to

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Section: Resultsmentioning

confidence: 90%

A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments

Steinmetz¹,

Altenburger²,

Zachau³

1980

Nucl Acids Res

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“…Repetitive sequences (unidentified) were found when nick-translated wild-type genomic DNA was hybridized to restriction fragments immobilized on nitrocellulose (data not shown). Under the conditions used, only sequences present in over 100 copies per genome could be detected (28). Their location is shown in Fig.…”

Section: Resultsmentioning

confidence: 97%

Cellular DNA rearrangements and early developmental arrest caused by DNA insertion in transgenic mouse embryos.

Covarrubias¹,

Nishida²,

Terao³

et al. 1987

Mol. Cell. Biol.

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Insertional mutagenesis was investigated in a transgenic mouse strain (HUGH/4) derived from a fertilized egg injected with plasmid DNA containing the human growth hormone gene. Lethality occurred in homozygous embryos and was traced to the egg cylinder stage on days 4 to 5 of gestation, shortly after implantation. The mutation is on chromosome 12 and is distinct in location and integration pattern from another mutation also leading to lethality of homozygotes in the egg cylinder stage. Based on this and other evidence, relatively many genes may be recruited to activity near the time of implantation and may therefore present a large target of vulnerability to mutagenesis. The single insert in HUGH/4, consisting of approximately three tandem copies of plasmid sequences, is flanked by mouse cellular sequences that have undergone rearrangements, including a probable deletion. The data suggest the hypothesis that DNA rearrangements, which appear to be commonplace in transgenic mice, may arise because the initial insertional complex is unstable; stepwise changes may then be generated until a more stable conformation is achieved.

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“…The hybridization conditions only permitted detection of sequences present at more than 100 copies per genome (12). Fragment HUGH/3-1 lacks repetitive sequences within its 5-6 kb of mouse DNA.…”

Section: And 4) Evidence Inmentioning

confidence: 99%

Early postimplantation embryo lethality due to DNA rearrangements in a transgenic mouse strain.

Covarrubias¹,

Nishida²,

Mintz³

1986

Proc. Natl. Acad. Sci. U.S.A.

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Insertional mutagenesis in a transgenic mouse strain (HUGH/3) was caused by integration of plasmid DNA containing the human growth hormone gene and pBR322 plasmid sequences. From this study, which includes another instance of mutagenesis, and from other reports, it is apparent that insertional mutagenesis occurs fairly frequently during DNA integration in the mouse egg and that it is not specific for the exogenous DNA employed. The mutation in HUGH/3 is recessive and results in death of embryos homozygous for the donor sequences shortly after implantation, at the egg cylinder stage on days 4-5 of gestation. Restriction mapping ofthe insert and ofthe flanking DNA regions indicates that integration must have involved a series of complex events. Approximately five copies of plasmid sequences are arrayed in tandem but are interrupted at least twice by mouse cellular sequences. In addition, the mouse flanking DNA shows extensive rearrangements, probably including a deletion of at least 10 kilobases. The rearrangements may reflect an initially unstable DNA structure followed by attainment of a more stable conformation.

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Cloning of V region fragments from mouse liver DNA and localization of repetitive DNA sequences in the vicinity of immunoglobulin gene segments

Cited by 29 publications

References 18 publications

A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments

A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments

Cellular DNA rearrangements and early developmental arrest caused by DNA insertion in transgenic mouse embryos.

Early postimplantation embryo lethality due to DNA rearrangements in a transgenic mouse strain.

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