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A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

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A humanized mouse model for the reduced folate carrier.

David Patterson¹, Christine Graham, Christina Cherian

¹Eleanor Roosevelt Institute, Department of Biological Sciences, University of Denver, 1899 Gaylord Street, Denver, CO 80206, USA. dpatter2@du.edu

Molecular Genetics and Metabolism

|November 7, 2007

Summary

Researchers developed humanized mouse models to study the reduced folate carrier (RFC) gene. These models mimic human RFC expression, enabling in vivo analysis of folate transport and its impact on health and disease.

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Area of Science:

Molecular Biology
Genetics
Physiology

Background:

The reduced folate carrier (RFC), or SLC19A1, is crucial for folate transport in mammalian cells and tissues.
RFC facilitates essential functions like nutrient absorption, renal transport, and folate passage across the blood-brain barrier.

Purpose of the Study:

To create and characterize humanized mouse models for studying the human RFC (hRFC) gene in vivo.
To enable detailed investigation of hRFC gene regulation, expression, and its role in folate homeostasis and disease.

Main Methods:

Production and characterization of transgenic mice (TghRFC1) with a functional hRFC gene.
Generation of humanized mice by inactivating the mouse RFC (mRFC) gene and introducing an active hRFC gene.
Real-time RT-PCR analysis to assess tissue-specific expression of hRFC transcripts.

Main Results:

Humanized mice were healthy and bred successfully, exhibiting hRFC gene expression patterns similar to human tissues.
Predominant expression of B and A1/A2 5' UTRs was observed in humanized mice, mirroring human expression profiles.
Lower levels of A and C 5' UTRs were also detected, confirming complex hRFC gene regulation.

Conclusions:

Humanized mouse models provide a powerful platform for in vivo research on hRFC gene function and regulation.
These models facilitate the study of environmental and genetic factors influencing folate transport and distribution.
The availability of these models will advance understanding of human health and disease related to folate metabolism.