Editing Laboratory mouse (section)

===Tg2576===
A useful model for [[Alzheimer's disease]] (AD) in the lab is the Tg2576 strain of mice. The K670M and N671L double [[mutations]] seen in the human 695 splice-variant of the [[amyloid precursor protein]] (APP) are expressed by this strain. A [[hamster]] [[prion protein]] [[gene promoter]], predominantly in neurons, drives the expression. When compared to non-transgenic littermates, Tg2576 mice show a five-fold rise in Aβ40 and a 10- to 15-fold increase in Aβ42/43.<ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tg2576-mouse#:~:text=Tg2576%20mice%20exhibit%20many%20behavioral,70%2C%2072%E2%80%9375) | title=Tg2576 Mouse - an overview &#124; ScienceDirect Topics }}</ref><ref>{{cite journal | doi=10.1007/s11357-021-00401-6 | title=Early manifestation of gait alterations in the Tg2576 mouse model of Alzheimer's disease | date=2021 | last1=Nyul-Toth | first1=Adam | last2=Delfavero | first2=Jordan | last3=Mukli | first3=Peter | last4=Tarantini | first4=Amber | last5=Ungvari | first5=Anna | last6=Yabluchanskiy | first6=Andriy | last7=Csiszar | first7=Anna | last8=Ungvari | first8=Zoltan | last9=Tarantini | first9=Stefano | journal=Geroscience | volume=43 | issue=4 | pages=1947–1957 | pmid=34160781 | pmc=8492885 }}</ref><ref>{{cite journal | url=https://www.sciencedirect.com/science/article/pii/S0197458022002536 | doi=10.1016/j.neurobiolaging.2022.11.017 | title=Neuronal hyperexcitability in the Tg2576 mouse model of Alzheimer's disease – the influence of sleep and noradrenergic transmission | date=2023 | last1=b． Szabo | first1=Anna | last2=Cattaud | first2=Vanessa | last3=Bezzina | first3=Charlotte | last4=Dard | first4=Robin F. | last5=Sayegh | first5=Fares | last6=Gauzin | first6=Sebastien | last7=Lejards | first7=Camille | last8=Valton | first8=Luc | last9=Rampon | first9=Claire | last10=Verret | first10=Laure | last11=Dahan | first11=Lionel | journal=Neurobiology of Aging | volume=123 | pages=35–48 | pmid=36634385 }}</ref> These mice develop senile plaques linked to cellular inflammatory responses because their brains have approximately five times as much transgenic mutant human APP than indigenous mouse APP. The mice exhibit main characteristics of Alzheimer's disease (AD), such as increased generation of [[amyloid fibrils]] with aging, plaque formation, and impaired [[hippocampus]] learning and memory. Tg2576 mice are a good model for early-stage AD because they show amyloidogenesis and working memory impairments  linked to age but do not show neuronal degeneration.<ref name="Transgenic Mouse Models of Alzheime">{{cite journal | doi=10.3390/ijms23105404 | doi-access=free | title=Transgenic Mouse Models of Alzheimer's Disease: An Integrative Analysis | date=2022 | last1=Sanchez-Varo | first1=Raquel | last2=Mejias-Ortega | first2=Marina | last3=Fernandez-Valenzuela | first3=Juan Jose | last4=Nuñez-Diaz | first4=Cristina | last5=Caceres-Palomo | first5=Laura | last6=Vegas-Gomez | first6=Laura | last7=Sanchez-Mejias | first7=Elisabeth | last8=Trujillo-Estrada | first8=Laura | last9=Garcia-Leon | first9=Juan Antonio | last10=Moreno-Gonzalez | first10=Ines | last11=Vizuete | first11=Marisa | last12=Vitorica | first12=Javier | last13=Baglietto-Vargas | first13=David | last14=Gutierrez | first14=Antonia | journal=International Journal of Molecular Sciences | volume=23 | issue=10 | page=5404 | pmid=35628216 | pmc=9142061 | hdl=10261/306908 | hdl-access=free }}</ref> The absence of cell death suggests that changes in typical cellular signaling cascades involved in learning and synaptic plasticity are probably linked to the memory phenotype. Associative learning impairments are exacerbated when Tg2576 mice are crossed with PS1 transgenic animals that possess the A246E FAD mutation. This crosses promotes the build-up of amyloid and plaque development in the CNS.<ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tg2576-mouse#:~:text=Tg2576%20mice%20exhibit%20many%20behavioral,70%2C%2072%E2%80%9375) | title=Tg2576 Mouse - an overview &#124; ScienceDirect Topics }}</ref> This lends credence to the theory that AD [[pathogenesis]] is influenced by the interplay between APP and PS-1 gene products. Although Tg2576 mice do not perfectly replicate late-stage AD with cell death, they do offer a platform for researching the physiology and biochemistry of the illness. With the help of transgenic mouse models, researchers can make progress in AD research by understanding the intricate relationships between gene products that are involved in the production of Aβ peptide.e physiology and biochemistry of the illness.<ref name="Transgenic Mouse Models of Alzheime"/><ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tg2576-mouse#:~:text=Tg2576%20mice%20exhibit%20many%20behavioral,70%2C%2072%E2%80%9375) | title=Tg2576 Mouse - an overview &#124; ScienceDirect Topics }}</ref>