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Associated Chromosome Trap for Identifying Long-range DNA Interactions
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Associated Chromosome Trap for Identifying Long-range DNA Interactions

Published on: April 23, 2011

Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4a and p19ARF, is a candidate for the plasmacytoma

S Zhang1, E S Ramsay, B A Mock

  • 1Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 16, 1998
PubMed

Insights

Genetic control of plasma cell tumors in mice involves multiple genes. The study identifies a defective p16(INK4a) allele in susceptible BALB/c mice, suggesting it

Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • Plasma cell tumor (PCT) development in mice, induced by pristane, is influenced by multiple genes.
  • BALB/c mice are susceptible to PCT development, while DBA/2 mice are resistant, indicating a genetic basis for susceptibility.

Purpose of the Study:

  • To identify the genetic loci controlling susceptibility to pristane-induced PCT.
  • To investigate the role of cyclin-dependent kinase (CDK) inhibitors, specifically p16(INK4a), in PCT development.

Main Methods:

  • Utilized restriction fragment length polymorphisms (RFLPs) to map specific gene loci.
  • Employed sequencing of p16 and p18 cDNAs to identify allelic variants.
  • Conducted kinase assays using retinoblastoma protein to assess the inhibitory activity of p16 variants.

Main Results:

  • The Pctr1 locus, associated with PCT susceptibility, was mapped to chromosome 4.
  • Congenic strains revealed that DBA/2 alleles confer resistance, linked to CDK4/CDK6 inhibitors p16 and p15.
  • BALB/c mice possess distinct p16 allelic variants (A134C, G232A) that exhibit reduced inhibition of cyclin D2/CDK4 activity.

Conclusions:

  • A defective BALB/c-specific p16(INK4a) allele impairs inhibition of cyclin D2/CDK4, contributing to plasmacytoma susceptibility.
  • p16(INK4a) is a strong candidate gene for the Pctr1 locus, playing a critical role in the genetic control of PCT.

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