Surreal illustration of DNA strands forming animal silhouettes, representing Fanconi anemia research.

Decoding Fanconi Anemia: What Animal Models Reveal About This Rare Disease

Theo Raines in Health & Wellness December 2025 • 4 min read.

"From zebrafish to nematodes, animal models are helping researchers unravel the complexities of Fanconi anemia and paving the way for new treatments."

Fanconi anemia (FA) is a rare genetic disorder that affects multiple systems in the body, leading to bone marrow failure, birth defects, and an increased risk of cancer. Understanding this complex disease requires a multi-faceted approach, and animal models have proven invaluable in unraveling its mysteries.

While studying cells in the lab provides important information, it can't fully replicate the complexities of a living organism. Certain biological processes, such as blood cell development and the intricate cell divisions during meiosis, are incredibly difficult to mimic in a controlled setting. This is where animal models come in, allowing researchers to study FA within the context of a whole organism.

This article will explore how different animal models – from the humble nematode to the more complex zebrafish and mouse – have contributed to our understanding of FA, shedding light on the functions of the genes involved and revealing potential therapeutic targets. We'll also discuss the challenges and controversies that have emerged along the way.

Why Can't We Just Study Human Cells? The Power of In Vivo Models

Surreal illustration of DNA strands forming animal silhouettes, representing Fanconi anemia research.

The study of mutated proteins in cells outside a living organism is important. However, these studies cannot fully explain a disease. Certain physiological processes are difficult to reproduce in a lab setting. Animal models are valuable tools to study organisms and supplement cell studies.

Since the initial discovery of Fanconi anemia (FA) and the subsequent identification of the 19 FANC genes (FANCA to FANCT), researchers have been working to understand how these genes function and contribute to the disease. The current model suggests that these proteins work together in a single pathway, known as FA-BRCA, to repair a specific type of DNA damage called interstrand crosslinks (ICLs).

The FA-BRCA Pathway: This pathway is essential for repairing DNA damage caused by crosslinking agents.
ICLs and Their Impact: ICLs are particularly harmful to cells because they disrupt DNA replication and transcription.
The Role of FANC Proteins: These proteins participate in other cellular processes such as apoptosis (programmed cell death), cell cycle control, telomere maintenance, and cytokinesis (cell division).

The FA-BRCA pathway involves several steps. First, a complex of eight proteins (FANCA, -B, -C, -E, -F, -G, -L, and -M) forms in the nucleus, which activates FANCL, an enzyme that attaches ubiquitin to the FANCI-FANCD2 complex. This complex then relocates to the damaged DNA, coordinating with nucleases to unhook the ICL. The DNA is then repaired using translesion synthesis and homologous recombination, with proteins like FANCD1/BRCA2, FANCN/PALB2, FANCO/RAD51C, FANCR/RAD51, and FANCS/BRCA1 completing the repair.

The Future of FA Research: A Combined Approach

Animal models have been instrumental in revealing the involvement of the FA-BRCA pathway in various biological processes. These include stem cell survival, apoptosis, tumor prevention, and the repair of DNA damage from alcohol metabolism and oxidative stress.

Looking ahead, key questions remain about the biological and biochemical underpinnings of FA, the reasons for cancer predisposition, the causes of perinatal mortality (which are absent in some mouse models), the different cases of sex reversal in mice and zebrafish, and the developmental defects associated with the disease.

By studying the FANC proteins and understanding the phenotypic differences between humans and other in vivo systems, this research has greatly improved the understanding of the FA-BRCA pathway. The diversity in the use of different models is the source of new discoveries.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1051/medsci/20163206023, Alternate LINK

Title: Les Modèles Animaux De L’Anémie De Fanconi

Subject: General Biochemistry, Genetics and Molecular Biology

Journal: médecine/sciences

Publisher: EDP Sciences

Authors: Émilie L. Dubois, Mariline Béliveau, Jean-Yves Masson

Published: 2016-06-01

Everything You Need To Know

Why are animal models necessary to study Fanconi anemia instead of just using human cells in a lab?

Animal models, like zebrafish and nematodes, are crucial for understanding Fanconi anemia because they allow researchers to study the disease within a complete living system. Unlike studying cells in a lab, animal models enable the observation of complex biological processes such as blood cell development and meiosis, which are difficult to replicate in a controlled environment. This in vivo approach provides insights into how the FANC genes and the FA-BRCA pathway function in the context of an entire organism, revealing potential therapeutic targets that might be missed in simpler cell-based studies.

Why is the FA-BRCA pathway so important in understanding Fanconi anemia?

The FA-BRCA pathway is vital because it repairs DNA damage caused by interstrand crosslinks (ICLs). ICLs are particularly dangerous because they disrupt DNA replication and transcription, potentially leading to cell death or uncontrolled cell growth. The FA-BRCA pathway, involving proteins like FANCA, FANCI, and FANCD2, coordinates with nucleases to unhook these ICLs, followed by DNA repair mechanisms such as translesion synthesis and homologous recombination, which involve proteins like FANCD1/BRCA2 and FANCN/PALB2. Without a functional FA-BRCA pathway, cells accumulate DNA damage, increasing the risk of bone marrow failure, birth defects, and cancer, all characteristic of Fanconi anemia.

Besides DNA repair, what other cellular processes are the FANC proteins involved in, and how does this affect Fanconi anemia?

The different FANC proteins participate in a wide range of cellular processes beyond DNA repair. For example, they influence apoptosis (programmed cell death), cell cycle control, telomere maintenance, and cytokinesis (cell division). The FA-BRCA pathway’s involvement in stem cell survival, tumor prevention, and repair of DNA damage from alcohol metabolism and oxidative stress highlights its broad impact on cell health and genomic stability. Studying these varied roles in animal models provides a more complete picture of how defects in FANC proteins contribute to the diverse symptoms observed in Fanconi anemia patients.

How do mutations in the FANC genes lead to Fanconi anemia, and what role does the FA-BRCA pathway play in this process?

While mutations in the FANC genes (FANCA to FANCT) are a primary cause, the resulting disruption of the FA-BRCA pathway is the key mechanism leading to Fanconi anemia. This pathway is responsible for repairing interstrand crosslinks (ICLs) in DNA. When FANC proteins are defective, the FA-BRCA pathway cannot properly repair ICLs, leading to genomic instability and increased cell death or uncontrolled proliferation. Animal models help researchers understand how specific mutations in different FANC genes impact the overall function of the FA-BRCA pathway, thus linking genotype to phenotype in Fanconi anemia.

Can you explain in detail the steps of the FA-BRCA pathway and why understanding each step is important?

The FA-BRCA pathway involves a complex series of steps initiated by a complex of eight proteins (FANCA, -B, -C, -E, -F, -G, -L, and -M). This complex activates FANCL, which then ubiquitinates the FANCI-FANCD2 complex. This ubiquitinated complex relocates to the site of DNA damage, coordinating with nucleases to unhook the ICL. Subsequent repair involves translesion synthesis and homologous recombination, utilizing proteins such as FANCD1/BRCA2, FANCN/PALB2, FANCO/RAD51C, FANCR/RAD51, and FANCS/BRCA1. Understanding these steps is crucial for developing targeted therapies that can address specific points of failure within the pathway, potentially improving treatment outcomes for Fanconi anemia.