Isolation and mapping of four new DNA markers from mouse Chromosome 4

Krall, Marianne; Ruff, Naomi; Zimmerman, Kristi L.; Aggarwal, Archana; Dosik, Jennifer K.; Reeves, Roger H.; Mock, Beverly A.

doi:10.1007/bf00352484

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Backcross mice were bred and maintained in conventional closed barrier conditions at PerImmune (Rockville, MD) under National Cancer Institute Contract NO1-BC-21075. DNA isolation, restriction enzyme digestion, agarose gel electrophoresis, Southern blotting, and restriction fragment length polymorphism analyses were performed as described (3,10,11). DNA probes for Ifna, Mtv13, D4Lgm1, D4Rck41, Ccnb1-rs10, Tal2, Gt10, and Nppa were described previously (3,12).…”

Section: Methodsmentioning

confidence: 99%

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16^INK4aand p19^ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Zhang

Ramsay

Mock

1998

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

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133

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Plasma cell tumor induction in mice by pristane is under multigenic control. BALB͞c mice are susceptible to tumor development; whereas DBA͞2 mice are resistant. Restriction fragment length polymorphisms between BALB͞c and DBA͞2 for Cdkn2a(p16) and Cdkn2b(p15), and between BALB͞c and Mus spretus for Cdkn2c(p18 INK4c ) were used to position these loci with respect to the Pctr1 locus. These cyclin-dependent kinase (CDK) inhibitors mapped to a 6 cM interval of chromosome 4 between Ifna and Tal1. C.D2-Chr 4 congenic strains harboring DBA͞2 alleles associated with the Pctr1 locus contained DBA͞2 ''resistant'' alleles of the CDK4͞CDK6 inhibitors p16 and p15. On sequencing p16 and p18 cDNAs, two different allelic variants within ankyrin repeat regions of p16 were found between BALB͞c and DBA͞2 mice. By using an assay involving PCR amplification and restriction enzyme digestion, allelic variants were typed among several inbred strains of mice. One of the variants, G232A, was specific to two inbred strains, BALB͞cAn and ABP͞Le, of mice and occurred in a highly conserved amino acid in both human and rat p16. When tested with wild-type (DBA͞2) p16, both A134C and G232A BALB͞ c-specific variants of p16 were inefficient in their ability to inhibit the activity of cyclin D2͞CDK4 in kinase assays with retinoblastoma protein, suggesting this defective, inherited allele plays an important role in the genetic susceptibility of BALB͞c mice for plasmacytoma induction and that p16 INK4a is a strong candidate for the Pctr1 locus.

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Section: Methodsmentioning

confidence: 99%

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16^INK4aand p19^ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Zhang

Ramsay

Mock

1998

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

Self Cite

133

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“…The allele sizes of these SSLPs are available from the Massachusetts Institute of Technology Genome Center database. Probes for CD301, D4Lgm4, Mupl, Orm2, Jun, Ifa, and Scl have been previously described (3,15,16,20,21,25,27).…”

Section: Materuils and Methodsmentioning

confidence: 99%

Construction of a BALB/c congenic mouse, C.C3H-Lpsd, that expresses the Lpsd allele: analysis of chromosome 4 markers surrounding the Lps gene

et al. 1994

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Development of a congenic BALB/c mouse strain that contains a segment of chromosome 4 including the Lpsd allele of the lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ strain is presented. On the basis of LPS-induced spleen cell mitogenesis, macrophage tumor necrosis factor secretion, and tyrosine phosphorylation in vitro and lethality in galactosamine-sensitized mice in vivo, the C.C3H-Lpsd strain provides a model of LPS hyporesponsiveness that is comparable to that of the parental C3H/HeJ strain. Analysis of markers in this region indicates that length of the donor fragment is-5.5 centimorgans. Thus, the C.C3H-Lps" strain provides an important genetic tool for analysis of markers in this region and for examining functional effects of Lpsd expression on the BALB/c background.

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“…Plasmacytomagenesis in BALB/cAn mice is a complex genetic trait with 40%-60% penetrance in nonspecific pathogen free mice [5] . Through our genome-wide mapping studies utilizing genetic crosses with DBA/2 mice (0% tumor incidence), together with the development and use of a series of C.D2 congenic strains, coupled with representational difference analysis and positional cloning, we determined that Cdkn2a (p16), Mtor, and Mndal contribute to PCT susceptibility and resistance [Figures 1 and 2] [4][5][6][7][8][9][10][11] . Pctr1-2 are localized in non-contiguous, non-overlapping segments of mouse Chr 4, and Pctm, a modifier of PCT, on Chr 1.…”

Section: Experimental System: Identification Of Mouse Tumor Susceptibmentioning

confidence: 99%

Mouse tumor susceptibility genes identify drug combinations for multiple myeloma

Zhang¹,

Dubois²,

Zhang³

et al. 2020

JCMT

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Long-term genetic studies utilizing backcross and congenic strain analyses coupled with positional cloning strategies and functional studies identified Cdkn2a, Mtor, and Mndal as mouse plasmacytoma susceptibility/ resistance genes. Tumor incidence data in congenic strains carrying the resistance alleles of Cdkn2a and Mtor led us to hypothesize that drug combinations affecting these pathways are likely to have an additive, if not synergistic effect in inhibiting tumor cell growth. Traditional and novel systems-level genomic approaches were used to assess combination activity, disease specificity, and clinical potential of a drug combination involving rapamycin/ everolimus, an Mtor inhibitor, with entinostat, an histone deacetylase inhibitor. The combination synergistically repressed oncogenic MYC and activated the Cdkn2a tumor suppressor. The identification of MYC as a primary upstream regulator led to the identification of small molecule binders of the G-quadruplex structure that forms in the NHEIII region of the MYC promoter. These studies highlight the importance of identifying drug combinations which simultaneously upregulate tumor suppressors and downregulate oncogenes.

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Isolation and mapping of four new DNA markers from mouse Chromosome 4

Cited by 7 publications

References 7 publications

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16^INK4aand p19^ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16^INK4aand p19^ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Construction of a BALB/c congenic mouse, C.C3H-Lpsd, that expresses the Lpsd allele: analysis of chromosome 4 markers surrounding the Lps gene

Mouse tumor susceptibility genes identify drug combinations for multiple myeloma

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Isolation and mapping of four new DNA markers from mouse Chromosome 4

Cited by 7 publications

References 7 publications

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4aand p19ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4aand p19ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Construction of a BALB/c congenic mouse, C.C3H-Lpsd, that expresses the Lpsd allele: analysis of chromosome 4 markers surrounding the Lps gene

Mouse tumor susceptibility genes identify drug combinations for multiple myeloma

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Product

Resources

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Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16^INK4aand p19^ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16^INK4aand p19^ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1