MARK1, short for microtubule affinity regulating kinase 1, is a protein-coding gene with a crucial role in various biological processes. It has been implicated in neurodevelopmental disorders, and its accelerated evolution in the human lineage suggests a role in cognition. It is also involved in pathways related to cell migration, cancer progression, and lung development [1-5, 7-9]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying MARK1's functions.

In KO/CKO mouse models, forebrain-specific conditional knockout of Mark1 in mice leads to defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons, reducing spine density. These mice also show spatial learning defects in the Morris water maze and reduced anxiety-like behaviors in the elevated plus maze. Additionally, loss of MARK1 causes synaptic accumulation of GKAP and GluA2, indicating its role in synaptic function [1,2]. In lung development, Mark1-knockout mice have impaired distal sacculation and type I pneumocyte (AECI) flattening, as fibroblasts expressing Mark1 are required for the terminal stages of pulmonary development [3].

In conclusion, MARK1 plays essential roles in regulating dendritic spine morphogenesis and cognitive functions in the nervous system, as well as in distal lung sacculation during lung development. The KO/CKO mouse models have significantly contributed to understanding its functions in these specific disease-relevant areas, such as neurodevelopmental disorders and potential lung-related pathologies associated with abnormal lung development.