Four Core Genotypes mouse model: localization of the Sry transgene and bioassay for testicular hormone levels
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BACKGROUND: The "four core genotypes" (FCG) mouse model has emerged as a major model testing if sex differences in phenotypes are caused by sex chromosome complement (XX vs. XY) or gonadal hormones or both. The model involves deletion of the testis-determining gene Sry from the Y chromosome and insertion of an Sry transgene onto an autosome. It produces XX and XY mice with testes, and XX and XY mice with ovaries, so that XX and XY mice with the same type of gonad can be compared to assess phenotypic effects of sex chromosome complement in cells and tissues. FINDINGS: We used PCR to amplify the Sry transgene and adjacent genomic sequences, to resolve the location of the Sry transgene to chromosome 3 and confirmed this location by fluorescence in situ hybridization (FISH) of the Sry construct to metaphase chromosomes. Using quantitative PCR, we estimate that 12-14 copies of the transgene were inserted. The anogenital distance (AGD) of FCG pups at 27-29 days after birth was not different in XX vs. XY males, or XX vs. XY females, suggesting that differences between XX and XY mice with the same type of gonad are not caused by difference in prenatal androgen levels. CONCLUSION: The Sry transgene in FCG mice is present in multiple copies at one locus on chromosome 3, which does not interrupt known genes. XX and XY mice with the same type of gonad do not show evidence of different androgen levels prenatally.
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The FCG mouse model allows for an independent assessment of gonadal hormones and sex chromosomal effects.
“we used the Four Core Genotypes (FCG) mouse model, which allows for an independent assessment of gonadal hormones and sex chromosomal effects [47–49].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [47]
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- Authors
- Itoh, Y., Mackie, R., Kampf, K., Domadia, S., Brown, J. D., O’Neill, R., & Arnold, A. P.
- Affiliations
- University of California, Los Angeles (US)
- University of Connecticut (US)
- Corresponding author
- Arnold, Arthur P
- Venue
- BMC Research Notes
- Published
- 2015-03-07
- Volume
- 8
- Issue
- 1
- Pages
- 69-69
- ISSN
- 1756-0500 (ISSN-L)
- PMC
- PMC4354741
- OpenAlex
- W2000906752
- Cited by
- 109
- References
- 81
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 22 · 2023: 6 · 2022: 14 · 2021: 6 · 2020: 12 · 2019: 6 · 2018: 8 · 2017: 10 · 2016: 6 · 2015: 2
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Research Notes (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (DK 083561)
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK083561, R01DK083561, DK083561)
- National Institute of Neurological Disorders and Stroke (NS 043196, R01NS043196)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD076125, HD076125)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- testis-determining gene, sex chromosome complement, gonadal hormones, anogenital distance, transgene copy number, chromosome 3, sex differences in phenotype
- MeSH terms
- Androgens, Animals, Biological Assay, Female, Genotype, Male, Mice, Transgenic, Ovary, Phenotype, Sex Characteristics, Testis, X Chromosome, Y Chromosome, In Situ Hybridization, Fluorescence, Gene Dosage, Transgenes, Genes, sry, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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