Reference SummaryHaigis KM, Nat Genet 2003 Jan;33(1):33-9

Title

A Robertsonian translocation suppresses a somatic recombination pathway to loss of heterozygosity.

Authors

Haigis KM; Dove WF

Journal

Nat Genet

Volume

Issue

Year

2003

Pages

33-9

Abstract

In mammals, loss of APC/Apc gatekeeper function initiates intestinal tumorigenesis. Several different mechanisms have been shown or proposed to mediate functional loss of APC/Apc: mutation in APC/Apc, non-disjunction, homologous somatic recombination and epigenetic silencing. The demonstration that, in the C57BL/6 (B6) Apc(Min/+) mouse model of inherited intestinal cancer, loss of Apc function can occur by loss of heterozygosity (LOH) through somatic recombination between homologs presents an opportunity to search for polymorphisms in the homologous somatic recombination pathway. We report that the Robertsonian translocation Rb(7.18)9Lub (Rb9) suppresses the multiplicity of intestinal adenomas in this mouse model. As the copy number of Rb9 increases, the association with the interphase nucleolus of the rDNA repeats centromeric to the Apc locus on Chromosome 18 is increasingly disrupted. Our analysis shows that homologous somatic recombination is the principal pathway for LOH in adenomas in B6 Apc(Min/+) mice. These studies provide additional evidence that neoplastic growth can initiate in the complete absence of canonical genomic instability.

Links

J:80330 – MGI References
12447373 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
C57BL/6-Apc^Min/+	Background is mix of C57BL/6J and C57BL/6JEi purchased from Jackson cryopreservation facility. These mice are littermates to Apc^Min mice carrying Robertsonian translocation involving chromosomes 7 and 18 on the C57BL/6EiJ background.
C57BL/6-Apc^Min +/+ Rb(7.18)9Lub	These mice are part of littermate study to look at effects of Robertsonian translocations on tumor susceptability in Apc^Min mice.
C57BL/6-Apc^Min Rb(7.18)9Lub/+ +	These mice are part of littermate study to look at effects of Robertsonian translocations on tumor susceptability in Apc^Min mice.
C57BL/6-Apc^Min/+ Rb(7.18)9Lub	These mice are part of littermate study to look at effects of Robertsonian translocations on tumor susceptability in Apc^Min mice.

Models
Strain	Model Name	Organ Affected	Frequency
C57BL/6-Apc^Min/+	Intestine adenoma	Intestine	observed
C57BL/6-Apc^Min +/+ Rb(7.18)9Lub	Intestine adenoma	Intestine	observed
C57BL/6-Apc^Min Rb(7.18)9Lub/+ +	Intestine adenoma	Intestine	observed
C57BL/6-Apc^Min/+ Rb(7.18)9Lub	Intestine adenoma	Intestine	observed