TABLE 1.

Successful application of the 2nd generation mouse models.

(1) Behavioral analysis using IntelliCage (Masuda et al., 2016; Sutoko et al., 2021).

(2) Three-dimensional visualization of amyloid pathology by transparency (Hama et al., 2015; Susaki et al., 2020).

(3) Impairment of gamma oscillations in medial entorhinal cortex (Nakazono et al., 2017).

(4) Additional genetic manipulation of the 2nd generation models through genome editing (Nagata et al., 2018; Watamura et al., 2021b).

(5) Generation of the double knock-in mouse models (Hashimoto et al., 2019; Saito et al., 2019; Sato et al., 2021).

(6) Assessment of vascular dysfunction in the 2nd generation models (Nortley et al., 2019; Tachida et al., 2020).

(7) Assessment of sleep dysfunction in the 2nd generation models (Maezono et al., 2020).

(8) Assessment of place cell dysfunction in the 2nd generation models (Jun et al., 2020; Takamura et al., 2021).

(9) Analyses of various aspects of neuroinflammation (Shirotani et al., 2019; Chiasseu et al., 2020; Salobrar-García et al., 2020; Barrett et al., 2021; Sobue et al., 2021).

(10) Application of spatial transcriptomics (Chen et al., 2020).