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Nf1 expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studies

Affiliation

  • 1 Mouse Cancer Genetics Program, National Cancer Institute-Frederick, West 7th Street at Fort Detrick, P.O. Box B, Building 560, Rm 31-20, Frederick, MD 21702, USA.
  • PMID: 17216419
  • PMCID: PMC6687394
  • DOI: 10.1007/s10048-006-0078-5

Free PMC article

Nf1 expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studies

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Authors

Affiliation

  • 1 Mouse Cancer Genetics Program, National Cancer Institute-Frederick, West 7th Street at Fort Detrick, P.O. Box B, Building 560, Rm 31-20, Frederick, MD 21702, USA.
  • PMID: 17216419
  • PMCID: PMC6687394
  • DOI: 10.1007/s10048-006-0078-5

Abstract

Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the nervous system, with elevated risk for both astrocytoma and peripheral nerve sheath tumors. NF1 is caused by a germline mutation in the NF1 gene, with tumors showing loss of the wild type copy of NF1. In addition, NF1 heterozygosity in surrounding stroma is important for tumor formation, suggesting an additional role of haploinsufficiency for NF1. Studies in mouse models and NF1 families have implicated modifier genes unlinked to NF1 in the severity of the disease and in susceptibility to astrocytoma and peripheral nerve sheath tumors. To determine if differences in Nf1 expression may contribute to the strain-specific effects on tumor predisposition, we examined the levels of Nf1 gene expression in mouse strains with differences in tumor susceptibility using quantitative polymerase chain reaction. The data presented in this paper demonstrate that strain background has as much effect on Nf1 expression levels as mutation of one Nf1 allele, indicating that studies of haploinsufficiency must be carefully interpreted with respect to strain background. Because expression levels do not correlate entirely with the susceptibility or resistance to tumors observed in the strain, these data suggest that either variation in Nf1 levels is not responsible for the differences in astrocytoma and peripheral nerve sheath tumor susceptibility in Nf1-/+;Trp53-/+cis mice, or that certain mouse strains have evolved compensatory mechanisms for differences in Nf1 expression.

Figures

Comparison of nerve sheath tumor…

Comparison of nerve sheath tumor resistance loci, Nstr1 and Nstr2 , to quantitative…

Standard PCR annealing temperature gradients…

Standard PCR annealing temperature gradients from 50 to 70°C using Nf1 primer set…

qPCR of Nf1 ( a…

qPCR of Nf1 ( a ) and Nf1 exon 9a ( b )…

qPCR of Nf1 expression levels…

qPCR of Nf1 expression levels in the brains of astrocytoma susceptible ( susc…

Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the nervous system, with elevated risk for both astrocytoma and peripheral nerve sheath tumors. NF1 is caused by a germline mutation in the NF1 gene, with tumors showing loss of the wild type copy of NF1. In a …