Tracking of mouse cell lineage using microinjected DNA sequences: Analyses using genomic Southern blotting and tissue-section in situ hybridizations

Lo, Cecilia W.; Coulling, Margaret; Kirby, Colleen

doi:10.1111/j.1432-0436.1987.tb00149.x

Cited by 54 publications

(42 citation statements)

References 20 publications

(21 reference statements)

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“…Moreover, pronuclear injection of transgene into fertilized oocytes of MRL-Fas lpr mice was performed to maintain a complete host genetic background, thereby preventing any issues related to genetic background. Although there might be a concern about the effect of integration sites of BAC on function, especially when multiple copies have integrated, a genomic-integration site of the transgene is typically confined to a single genomic site, regardless of the copy numbers (25). Furthermore, we revealed two independent tg lines of each group to avoid the risk that a DNAintegration site might reflect on different phenotypes in each group, which showed similar autoimmunity and mortality.…”

Section: Discussionmentioning

confidence: 88%

A Bacterial Artificial Chromosome Transgene with PolymorphicCd72Inhibits the Development of Glomerulonephritis and Vasculitis in MRL-FaslprLupus Mice

Oishi

Tsubaki

Miyazaki

et al. 2013

The Journal of Immunology

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Systemic lupus erythematosus is considered to be under the control of polygenic inheritance, developing according to the cumulative effects of susceptibility genes with polymorphic alleles; however, the mechanisms underlying the roles of polygenes based on functional and pathological genomics remain uncharacterized. In this study, we substantiate that a CD72 polymorphism in the membrane-distal extracellular domain impacts on both the development of glomerulonephritis and vasculitis in a lupus model strain of mice, MRL/MpJ-Faslpr, and the reactivity of BCR signal stimulation. We generated mice carrying a bacterial artificial chromosome transgene originating from C57BL/6 (B6) mice that contains the Cd72b locus (Cd72B6 transgenic [tg]) or the modified Cd72b locus with an MRL-derived Cd72c allele at the polymorphic region corresponding to the membrane-distal extracellular domain (Cd72B6/MRL tg). Cd72B6 tg mice, but not Cd72B6/MRL tg mice, showed a significant reduction in mortality following a marked improvement of disease associated with decreased serum levels of IgG3 and anti-dsDNA Abs. The number of splenic CD4−CD8− T cells in Cd72B6 tg mice was decreased significantly in association with a reduced response to B cell receptor signaling. These results indicate that the Cd72 polymorphism affects susceptibility to lupus phenotypes and that novel functional rescue by a bacterial artificial chromosome transgenesis is an efficient approach with wide applications for conducting a genomic analysis of polygene diseases.

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Section: Discussionmentioning

confidence: 88%

A Bacterial Artificial Chromosome Transgene with PolymorphicCd72Inhibits the Development of Glomerulonephritis and Vasculitis in MRL-FaslprLupus Mice

Oishi

Tsubaki

Miyazaki

et al. 2013

The Journal of Immunology

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“…Because of the neonatal lethality of homozygous math1 null mice (math1 ␤-Gal/␤-Gal ), the mutant component of the chimeras was generated by mating math1 ␤-Gal/ϩ males and females to generate math1 ␤-Gal/␤-Gal , math1 ␤-Gal/ϩ , or math1 ϩ/ϩ embryos. The wild-type (ϩ/ϩ) component was generated from one of five different lines: ICR, Rosa26 (Friedrich and Soriano, 1991), Balb/c J , GTO (Lo et al, 1987), or math1 ϩ/ϩ . Experimental mouse chimeras were generated as described previously (Goldowitz and Mullen, 1982;Goldowitz, 1989).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Jensen¹,

Smeyne²,

Goldowitz³

2004

J. Neurosci.

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The cerebellar granule cell is the most numerous neuron in the nervous system and likely the source of the most common childhood brain tumor, medulloblastoma. The earliest known gene to be expressed in the development of these cells is math1. In the math1 null mouse, neuroblasts never populate the external germinal layer (EGL) that gives rise to granule cells. In this study, we examined the embryonic development of the math1 null cerebellum and analyzed experimental mouse chimeras made from math1 null embryos. We find that the anterior rhombic lip gives rise to more than one cell type, indicating that the rhombic lip does not consist of a homogeneous population of cells. Furthermore, we demonstrate that math1 null granule cells are absent in the math1 null chimeric cerebellum, from the onset of their genesis in the mouse anterior rhombic lip. This finding indicates a vital cell intrinsic role for Math1 in the granule cell lineage. In addition, we show that wild-type cells are unable to compensate for the loss of mutant cells. Finally, the colonization of the EGL by wild-type cells and the presence of acellular gaps provides evidence that EGL neuroblasts undergo active migration and likely have a predetermined spatial address in the rhombic lip.

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“…However, detecting GPI variants requires the destruction of tissues, which precludes detection of these variants at the spatial resolution needed to determine chimerism at the histological level. The first generation of genetic markers that were used for chimera analysis allowed cells of different origins to be distinguished by the presence of strain-specific DNA satellite markers (Rossant et al, 1983) or a large globin transgene insert (Lo et al, 1987). The use of these markers involves technically difficult DNA-DNA in situ hybridization of histological preparations of the embryo.…”

Section: Lineage Markers For Chimera Analysismentioning

confidence: 99%

Mouse embryonic chimeras: tools for studying mammalian development

2003

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Embryonic chimeras of the mouse are well-established tools for studying cell lineage and cell potential. They are also a key part of the analysis of complex phenotypes of mutant mice. By combining embryonic stem cell technology, molecularly tagged mutations and sensitive cell lineage markers,chimeras can provide invaluable insights into the tissue-specific requirement and the mode of action of many mouse genes.

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Tracking of mouse cell lineage using microinjected DNA sequences: Analyses using genomic Southern blotting and tissue-section in situ hybridizations

Cited by 54 publications

References 20 publications

A Bacterial Artificial Chromosome Transgene with PolymorphicCd72Inhibits the Development of Glomerulonephritis and Vasculitis in MRL-FaslprLupus Mice

A Bacterial Artificial Chromosome Transgene with PolymorphicCd72Inhibits the Development of Glomerulonephritis and Vasculitis in MRL-FaslprLupus Mice

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Mouse embryonic chimeras: tools for studying mammalian development

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