PT  - JOURNAL ARTICLE
AU  - Daniel R. Gulbranson
AU  - Kaitlyn Ho
AU  - Gui-Qiu Yu
AU  - Xinxing Yu
AU  - Melanie Das
AU  - Eric Shao
AU  - Daniel Kim
AU  - Weiping J. Zhang
AU  - Krishna Choudhary
AU  - Reuben Thomas
AU  - Lennart Mucke
TI  - Phenotypic Differences between the Alzheimer’s Disease-Related hAPP-J20 Model and Heterozygous <em>Zbtb20</em> Knock-Out Mice
AID  - 10.1523/ENEURO.0089-21.2021
DP  - 2021 May 01
TA  - eneuro
PG  - ENEURO.0089-21.2021
VI  - 8
IP  - 3
4099  - http://www.eneuro.org/content/8/3/ENEURO.0089-21.2021.short
4100  - http://www.eneuro.org/content/8/3/ENEURO.0089-21.2021.full
SO  - eNeuro2021 May 01; 8
AB  - Diverse gene products contribute to the pathogenesis of Alzheimer’s disease (AD). Experimental models have helped elucidate their mechanisms and impact on brain functions. Human amyloid precursor protein (hAPP) transgenic mice from line J20 (hAPP-J20 mice) are widely used to simulate key aspects of AD. However, they also carry an insertional mutation in noncoding sequence of one Zbtb20 allele, a gene involved in neural development. We demonstrate that heterozygous hAPP-J20 mice have reduced Zbtb20 expression in some AD-relevant brain regions, but not others, and that Zbtb20 levels are higher in hAPP-J20 mice than heterozygous Zbtb20 knock-out (Zbtb20+/–) mice. Whereas hAPP-J20 mice have premature mortality, severe deficits in learning and memory, other behavioral alterations, and prominent nonconvulsive epileptiform activity, Zbtb20+/– mice do not. Thus, the insertional mutation in hAPP-J20 mice does not ablate the affected Zbtb20 allele and is unlikely to account for the AD-like phenotype of this model.