A new family of interspersed repetitive DNA sequences in the mouse genome

Gebhard, Wolfgang; Meitinger, Thomas; Höchtl, Josef; Zachau, Hans G.

doi:10.1016/0022-2836(82)90471-5

Cited by 108 publications

(68 citation statements)

References 40 publications

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“…The MIF-1 sequences at the C3 and C6 junctions were 95 and 88% homologous, respectively, to the c d sequences described previously (5,12,14 (Fig. SB).…”

Section: Methodssupporting

confidence: 68%

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Foreign DNA introduced by calcium phosphate is integrated into repetitive DNA elements of the mouse L cell genome.

Kato¹,

Anderson²,

Camerini‐Otero³

1986

Mol. Cell. Biol.

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We investigated the sites of integration of exogenous DNA fragments introduced by DNA-mediated gene transfer. Mouse Ltk-cells were transformed with the herpes simplex virus thymidine kinase gene and pBR322 DNA by the calcium phosphate precipitation method. Some of the integrated exogenous DNA sequences were recovered from the stable tk+ transformants in the form of plasmids that were capable of propagation in bacteria. Four plasmids derived from two cloned cell lines were analyzed in detail by nucleotide sequencing and hybridization techniques. These plasmids contained a total of seven cellular-exogenous DNA junctions. In all cases, there was no sequence homology between the exogenous and cellular DNA sequences adjacent to the joining sites, and no specific exogenous or cellular sequences occurred at the junctions. Rearrangement or deletion of Ltk-DNA was always associated with the integration of exogenous DNA. All of the assignable cellular sequences at the junctions were repetitive sequences. Two of these sequences were from the MIF-1 repetitive sequence family, and a third consisted of a 40-base pair simple copolymer of alternating deoxyadenosine-deoxythymidine. Our results suggest that repetitive sequences are relatively favorable sites for the integration of exogenous DNA.Homologous recombination of foreign DNA with the host genome is sufficiently frequent in procaryotes (33) and lower eucaryotes (18) that it is possible to confidently predict the integration site of the introduced DNA. Since such efficient "targeting" of DNA into homologous sequences has not yet been demonstrated in mammalian cells (41), we asked whether the foreign DNA is integrated randomly or at some preferred sites other than the homologous sequences. Although a number of workers have reported on the DNA sequences at the integration sites of viral DNAs that have been introduced into mammalian cells (3,11,37,39), there have been no reports of a similar analysis for the integration of nonviral DNAs. Even though it has been established that at the level of chromosome analysis foreign, nonviral DNAs are integrated randomly (36), there is no information on the DNA sequences at the integration sites of exogenous nonviral DNAs.Since the site of integration may be influenced by proteins encoded by the DNA in question (as appears to be the case for the genomes of some eucaryotic viruses [34]) as opposed to DNA which relies solely on the cellular machinery for its integration, we examined integration sites resulting from the transfer of purified gene fragments and procaryotic DNA. Following transformation of mouse Ltk-cells with a herpes simplex virus thymidine kinase gene (tk) fragment and pBR322 DNA, individual colonies of stable tk+ transformants were isolated and expanded. A plasmid rescue technique was used to recover the integrated exogenous DNA and flanking cellular sequences from the genomic DNA of these cell lines (1, 2). We analyzed the sequences encompassing seven cellular-exogenous DNA junctions. MATERIALS AND METHODSDNA-mediated ge...

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“…The MIF-1 sequences at the C3 and C6 junctions were 95 and 88% homologous, respectively, to the c d sequences described previously (5,12,14 (Fig. SB).…”

Section: Methodssupporting

confidence: 68%

“…Extensive homologies exist between the cellular sequences at the C3 and C6 junctions and the sequence of MIF-1, a moderately repetitive DNA sequence family (5,12,14,30,50). Restriction maps of the rescued plasmids.…”

Section: Methodsmentioning

confidence: 99%

Foreign DNA introduced by calcium phosphate is integrated into repetitive DNA elements of the mouse L cell genome.

Kato¹,

Anderson²,

Camerini‐Otero³

1986

Mol. Cell. Biol.

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“…7). The 5' endpoints of two other instances of this repeat family within the immunoglobulin gene region have been sequenced as R family repeats and those endpoints are not the same (11).…”

Section: The Conserved Endpoint Of Llmdmentioning

confidence: 99%

“…Several groups (11,12,13,14) have characterized the repetitive sequences MIF-1, Bam-5, and R which are each found in different abundances in the mouse genome. While this variation in abundance leads to the natural assumption that the repetitive elements are independent of each other, a recent proposal links these repeats into a single unit which was called the BamHl family (24).…”

Section: Introductionmentioning

confidence: 99%

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The L1Md long interspersed repeat family in the mouse: almost all examples are truncated at one end

et al. 1983

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We have characterized a large repetitive element which has been found at seven different locations within the beta globin locus of the BALB/c mouse. This repeat has an unusual structure in that each of the different members has the same end of the element conserved while the other end terminates at a different point in each repeat member. The sequences within the repeats from the beta globin locus have homology with other repetitive families such as the MIF-1, Bam-5, R, and the BamHl families. These were recently proposed (T. Fanning, (1983) Nucleic Acids Res. 11, 5073-5091) to be part of a structure with the same organization which we found in the globin locus. Probing plaques from a BALB/c genomic library with sequences derived from the repeats in the globin locus shows that virtually all of the repeats from this family are organized in a manner consistent with the proposed structure.

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Coding joint formation of endogenous T cell receptor genes in lymphoid cells from scid mice: unusual P‐nucleotide additions in VJ‐coding joints

Schüler¹,

Amsler²,

Ruetsch

et al. 1991

Eur J Immunol

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The mouse mutation scid adversely affects the process of VDJ recombination. Attempts to form coding joints, that is, to joint V or D to J gene segments generally fail in developing scid lymphocytes. It has been proposed that the scid mutation results a defective VDJ recombinase system. Here we describe five scid T cell lymphomas containing one or two TcR gamma coding joints each, even though the majority of the multiple TcR gamma chain gene rearrangements and all TcR beta rearrangements in these cells were abnormal with the deletions typically found in scid lymphoid cells. One of the five T cell lymphomas was shown to have an active VDJ recombinase system; however, this activity was defective indicating that the scid phenotype has been retained. We conclude that the scid VDJ recombinase system has not completely lost the ability to form coding joints. P-nucleotide additions of unusual length or composition were found at the junctional border in five of the eight TcR gamma coding joints. This might reflect a defect in the activity of a component of the VDJ recombinase system involved in the generation of P-nucleotide additions. In one of the observed rearrangements, a V gamma 5-J gamma 3 coding joint was formed. This establishes the transcriptional orientation of J gamma 3-C gamma 3 and confirms a previously proposed organization of the TcR gamma genes.

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A new family of interspersed repetitive DNA sequences in the mouse genome

Cited by 108 publications

References 40 publications

Foreign DNA introduced by calcium phosphate is integrated into repetitive DNA elements of the mouse L cell genome.

Foreign DNA introduced by calcium phosphate is integrated into repetitive DNA elements of the mouse L cell genome.

The L1Md long interspersed repeat family in the mouse: almost all examples are truncated at one end

Coding joint formation of endogenous T cell receptor genes in lymphoid cells from scid mice: unusual P‐nucleotide additions in VJ‐coding joints

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