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

Area of Science:

• Genetics
• Immunology
• Reproductive Biology

Background:

• The Four Core Genotypes (FCG) mouse model is crucial for studying sex chromosome and hormone functions.
• Accurate interpretation of FCG studies relies on understanding genetic variations within the model.

Purpose of the Study:

• To identify and characterize a previously unreported genetic anomaly in the C57BL/6J FCG mouse model.
• To investigate the functional consequences of this anomaly on gene expression and its implications for research.

Main Methods:

• Utilized genomic analysis to detect chromosomal rearrangements.
• Quantified gene expression levels of X-linked genes, including Tlr7.
• Assessed the impact of the translocation on the interpretation of FCG studies.

Main Results:

• A 3.2 MB region of the X chromosome was found to have translocated to the Y chromosome (Y^Sry-).
• This translocation resulted in increased expression of X-linked genes, notably Tlr7, a sensor of single-stranded RNA and mediator of autoimmune disease.
• The presence of this X-Y translocation was confirmed as a novel finding in C57BL/6J FCG mice.

Conclusions:

• The identified X-Y translocation represents a significant genetic variation in the C57BL/6J FCG mouse model.
• This translocation complicates the interpretation of research findings that utilize this specific mouse model, particularly those investigating sex chromosome function and autoimmune responses.
• Researchers should be aware of this genetic anomaly when designing or interpreting studies involving C57BL/6J FCG mice to ensure accurate conclusions.