Fine map of the Gct1 spontaneous ovarian granulosa cell tumor locus

The spontaneous development of juvenile-onset, ovarian granulosa cell (GC) tumors in the SWR/Bm (SWR) inbred mouse strain is a model for juvenile-type GC tumors that appear in infants and young girls. GC tumor susceptibility is supported by multiple Granulosa cell tumor (Gct) loci, but the Gct1 locus on Chr 4 derived from SWR strain background is fundamental for GC tumor development and uniquely responsive to the androgenic precursor dehydroepiandrosterone (DHEA). To resolve the location of Gct1 independently from other susceptibility loci, Gct1 was isolated in a congenic strain that replaces the distal segment of Chr 4 in SWR mice with a 47 × 10(6)-bp genomic segment from the Castaneus/Ei (CAST) strain. SWR females homozygous for the CAST donor segment were confirmed to be resistant to DHEA- and testosterone-induced GC tumorigenesis, indicating successful exchange of CAST alleles (Gct1(CA)) for SWR alleles (Gct1(SW)) at this tumor susceptibility locus. A series of nested, overlapping, congenic sublines was created to fine-map Gct1 based on GC tumor susceptibility under the influence of pubertal DHEA treatment. Twelve informative lines have resolved the Gct1 locus to a 1.31 × 10(6)-bp interval on mouse Chr 4, a region orthologous to human Chr 1p36.22. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-012-9439-6) contains supplementary material, which is available to authorized users

Reproductive performance of alternative male phenotypes of growth hormone transgenic Atlantic salmon (Salmo salar)

Growth hormone (GH) transgenic Atlantic salmon (Salmo salar) is one of the first transgenic animals being considered for commercial farming, yet ecological and genetic concerns remain should they enter the wild and interact reproductively with wild fish. Here, we provide the first empirical data reporting on the breeding performance of GH transgenic Atlantic salmon males, including that of an alternative male reproductive phenotype (i.e. small, precocially mature parr), in pair-wise competitive trials within a naturalised stream mesocosm. Wild anadromous (i.e. large, migratory) males outperformed captively reared transgenic counterparts in terms of nest fidelity, quivering frequency and spawn participation. Similarly, despite displaying less aggression, captively reared nontransgenic mature parr were superior competitors to their transgenic counterparts in terms of nest fidelity and spawn participation. Moreover, nontransgenic parr had higher overall fertilisation success than transgenic parr, and their offspring were represented in more spawning trials. Although transgenic males displayed reduced breeding performance relative to nontransgenics, both male reproductive phenotypes demonstrated the ability to participate in natural spawning events and thus have the potential to contribute genes to subsequent generations

Chromosome X loci and spontaneous granulosa cell tumor development in SWR mice: epigenetics and epistasis at work for an ovarian phenotype.

Females of the SWR/Bm (SWR) inbred mouse strain possess a unique susceptibility to juvenile-onset tumors originating from the granulosa cells (GC) of the ovarian follicles. Tumor susceptibility is an inherited, polygenic trait in SWR females, minimally involving an oncogenic Granulosa cell tumor susceptibility (Gct) locus on chromosome (Chr) 4 (Gct1), and two GC tumor susceptibility modifier genes mapped to distinct regions of Chr X (Gct4 and Gct6). Shifts in the frequency of GC tumor initiation in the SWR female population from low penetrance to moderate penetrance, or phenotype switching between GC tumor-susceptible and GC tumor-resistant, is strongly influenced by the allelic contributions at Gct4 and Gct6. In addition to the allele-specific effects, GC tumor susceptibility is controlled by the mode of X-linked transmission with a dominant, paternal parent-of-origin effect. We took advantage of the robust paternal effect with a recombinant male progeny testing strategy to resolve the Gct4 locus interval to 1.345 million base (Mb) pairs. Based on the mapping resolution and the phenotype sensitivity to endogenous and exogenous androgen exposure, a promising candidate for Gct4 identity is the androgen receptor (Ar) gene. We explored the mechanism of allelic variation for Ar between SWR (low penetrance allele) and SJL/Bm (SJL) (moderate penetrance allele) using an SWR.SJL-X congenic strain resource and a quantitative gene expression method. We report the low GC tumor penetrance allele of the SWR strain correlates with significantly reduced Ar transcript levels in the female ovary at the pubertal transition. Epigenetics 2013 Feb; 8(2):184-91

Delayed Phenotypic Expression of Growth Hormone Transgenesis during Early Ontogeny in Atlantic Salmon (Salmo salar)?

Should growth hormone (GH) transgenic Atlantic salmon escape, there may be the potential for ecological and genetic impacts on wild populations. This study compared the developmental rate and respiratory metabolism of GH transgenic and non-transgenic full sibling Atlantic salmon during early ontogeny; a life history period of intense selection that may provide critical insight into the fitness consequences of escaped transgenics. Transgenesis did not affect the routine oxygen consumption of eyed embryos, newly hatched larvae or first-feeding juveniles. Moreover, the timing of early life history events was similar, with transgenic fish hatching less than one day earlier, on average, than their non-transgenic siblings. As the start of exogenous feeding neared, however, transgenic fish were somewhat developmentally behind, having more unused yolk and being slightly smaller than their non-transgenic siblings. Although such differences were found between transgenic and non-transgenic siblings, family differences were more important in explaining phenotypic variation. These findings suggest that biologically significant differences in fitness-related traits between GH transgenic and non-transgenic Atlantic salmon were less than family differences during the earliest life stages. The implications of these results are discussed in light of the ecological risk assessment of genetically modified animals

Lysozyme transgenic Atlantic salmon (Salmo salar L.)

10.1111/j.1365-2109.2010.02637.xAquaculture Research423427-440AQRE