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Research Paper

Chromosome X loci and spontaneous granulosa cell tumor development in SWR mice

Epigenetics and epistasis at work for an ovarian phenotype

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Pages 184-191 | Received 12 Oct 2012, Accepted 21 Dec 2012, Published online: 08 Jan 2013

Figures & data

Figure 1. Bilateral GC tumor specimen. Spontaneous GC tumors in SWR-derived mice are easily recognized as large, 5–15 mm cystic or solid masses with blood filled spaces when compared with a normal ovary of 2–3 mm. This image shows a representative bilateral GC tumor specimen with the uterus still attached. The specimen was isolated from an 8 wk old SWR.SJL-X3 congenic female that carries the Gct4J modifier allele. The GC tumor on the left is less vascularized and more necrotic than the larger, highly vascularized tumor on the right.

Figure 1. Bilateral GC tumor specimen. Spontaneous GC tumors in SWR-derived mice are easily recognized as large, 5–15 mm cystic or solid masses with blood filled spaces when compared with a normal ovary of 2–3 mm. This image shows a representative bilateral GC tumor specimen with the uterus still attached. The specimen was isolated from an 8 wk old SWR.SJL-X3 congenic female that carries the Gct4J modifier allele. The GC tumor on the left is less vascularized and more necrotic than the larger, highly vascularized tumor on the right.

Table 1. Ovarian GC tumor incidence in female offspring derived from SWR inbred, SWR.CAST-X congenic lines or reciprocal breeding crosses

Figure 2. Male mice carrying unique combinations of CAST and SWR genome in the region of the Gct4 locus on Chr X were mated to SWR dams and the GC tumor incidence measured in the F1 generation female offspring. White boxes represent SWR alleles present at the DNA marker or gene and black boxes represent CAST alleles. Of the haplotypes shown for six unique animals, males 3, 4 and 6 place the distal interval boundary for the moderate GC tumor susceptibility allele Gct4CA at 99.015 Mb (marker DXamd27), while male 5 places the proximal boundary of the interval at 97.670 Mb (DXamd3). Only male 4 carries the GC tumor susceptibility allele Gct4SW.

Figure 2. Male mice carrying unique combinations of CAST and SWR genome in the region of the Gct4 locus on Chr X were mated to SWR dams and the GC tumor incidence measured in the F1 generation female offspring. White boxes represent SWR alleles present at the DNA marker or gene and black boxes represent CAST alleles. Of the haplotypes shown for six unique animals, males 3, 4 and 6 place the distal interval boundary for the moderate GC tumor susceptibility allele Gct4CA at 99.015 Mb (marker DXamd27), while male 5 places the proximal boundary of the interval at 97.670 Mb (DXamd3). Only male 4 carries the GC tumor susceptibility allele Gct4SW.

Table 2. Candidate genes within the Gct4 locus interval

Figure 3. Quantitative expression of the Ar gene. Ovaries from a minimum of five individual females of the SWR and SWR.SJL-X5 strains were compared for quantitative expression of the Ar gene relative to the Actb reference gene by qPCR. A significantly increased expression was measured in the SWR.SJL-X5 ovaries, equal to 1.6 ± 0.13 fold that of the SWR strain (p = 0.0038).

Figure 3. Quantitative expression of the Ar gene. Ovaries from a minimum of five individual females of the SWR and SWR.SJL-X5 strains were compared for quantitative expression of the Ar gene relative to the Actb reference gene by qPCR. A significantly increased expression was measured in the SWR.SJL-X5 ovaries, equal to 1.6 ± 0.13 fold that of the SWR strain (p = 0.0038).
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