Macf1-flox Mouse

Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking factor 7 (ACF7), is a spectraplakin that plays a crucial role in coordinating cytoskeleton elements like actin microfilaments and microtubules. It is involved in multiple signaling pathways, such as the Wnt/β -catenin and GSK -3 signaling pathways, and is essential for various cellular processes including cell-cell connections, polarity, vesicular transport, proliferation, and migration [2,3].

Loss-of-function studies using knockout mouse models have revealed the significance of MACF1. In embryo development, it is pivotal [1]. In bone, conditional knockout (cKO) of mesenchymal Macf1 in mice led to decreased osteogenic differentiation, ossification retardation in early development, and attenuated bone mass and formation capability in adulthood. MACF1 promotes osteoblast differentiation by sequestering repressors in the cytoplasm, and enhances osteoblastic cell migration through regulating MAP1B via the GSK3β/TCF7 pathway [4,5,6]. In the nervous system, genetic mutation or dysregulation of MACF1 has been associated with neurodevelopmental and neurodegenerative diseases like schizophrenia and Parkinson's disease [2].

In conclusion, MACF1 is essential for normal functions in many tissues. KO/CKO mouse models have been instrumental in revealing its roles in embryo development, neural development, and bone-related processes. These findings contribute to understanding the pathogenesis of related diseases such as osteoporosis, schizophrenia, and Parkinson's disease, and suggest that MACF1 could be a potential therapeutic target for some of these conditions.