Four Core Genotypes mice harbour a 3.2MB X-Y translocation that perturbs Tlr7 dosage

Jasper Panten; Stefania Del Prete; James P Cleland; Lauren M Saunders; Job van Riet; Anja Schneider; Paul Ginno; Nina Schneider; Marie-Luise Koch; Xuqi Chen; Moritz Gerstung; Oliver Stegle; Arthur P Arnold; James M A Turner; Edith Heard; Duncan T Odom

doi:10.1038/s41467-024-52640-8

Four Core Genotypes mice harbour a 3.2MB X-Y translocation that perturbs Tlr7 dosage

Nat Commun. 2024 Oct 11;15(1):8814. doi: 10.1038/s41467-024-52640-8.

Authors

Jasper Panten^#^{1

2}, Stefania Del Prete^#¹, James P Cleland^#^{1

3}, Lauren M Saunders¹, Job van Riet^{1

4}, Anja Schneider¹, Paul Ginno¹, Nina Schneider¹, Marie-Luise Koch¹, Xuqi Chen⁵, Moritz Gerstung⁴, Oliver Stegle^{2

3}, Arthur P Arnold⁵, James M A Turner⁶, Edith Heard^{7

8}, Duncan T Odom⁹

Affiliations

¹ Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
⁴ Division of Artificial Intelligence in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Department of Integrative Biology & Physiology, University of California, Los Angeles, USA.
⁶ Sex Chromosome Biology Laboratory, The Francis Crick Institute, London, UK.
⁷ European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. [email protected].
⁸ Collège de France, Paris, France. [email protected].
⁹ Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany. [email protected].

^# Contributed equally.

Abstract

The Four Core Genotypes (FCG) is a mouse model system used to disentangle the function of sex chromosomes and hormones. We report that a copy of a 3.2 MB region of the X chromosome has translocated to the Y^Sry- chromosome and thus increased the expression of X-linked genes including the single-stranded RNA sensor and autoimmune disease mediator Tlr7. This previously-unreported X-Y translocation complicates the interpretation of studies reliant on C57BL/6J FCG mice.

MeSH terms

Animals
Female
Gene Dosage
Genotype*
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred C57BL*
Toll-Like Receptor 7* / genetics
Toll-Like Receptor 7* / metabolism
Translocation, Genetic*
X Chromosome* / genetics
Y Chromosome* / genetics

Substances

Toll-Like Receptor 7
Tlr7 protein, mouse
Membrane Glycoproteins