AMPA receptors (AMPARs) are excitatory neurotransmitter receptors and composed of four subunits (GluA1&ndash;4), with each subunit being coded by a different gene. The GluA2 subunit, encoded by the glutamate receptor, ionotropic, AMPA2 (alpha 2) (Gria2) gene, is essential for regulation of calcium permeability and transport. Gria2 mutations have been implicated in neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE) as well as neurodegenerative diseases such as Alzheimer's Disease. The Rosa26-stopflox-GluA2mut knock-in mouse model expresses two point mutations in the Gria2 gene; the L504Y mutation impairs AMPA receptor desensitization and the R845A blocks AMPA receptor endocytosis. These mutations are under the control of a floxed stop cassette. In the presence of Cre recombinase, the mutations are expressed and have been shown to enhance excitatory synaptic transmission. Homozygous Rosa26-stopflox-GluA2mut knock-in mice are viable with no overt phenotype; however, the donating investigator has indicated that homozygous mice do not breed when intercrossed. Homozygous females and homozygous males have successfully produced litters when mated to wildtype littermates or C57BL/6J mice. Heterozygous mice are viable with no fertility concerns. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will produce the GluA2 mutations in the cre-expressing tissues. These Rosa26-stopflox-GluA2mut knock-in mice may be useful for studying the role of Gria2 in neurodevelopmental disorders and neurodegenerative diseases. Note that based on sequencing analysis performed by The Jackson Laboratory, utilizing the Ensembl canonical transcript (<a href="https://useast.ensembl.org/Mus_musculus/Transcript/Summary?g=ENSMUSG00000033981;r=3:80588757-80710142;t=ENSMUST00000075316">Transcript: Gria2-201, ENSMUST00000075316.10</a>) as reference, the first amino acid substitution location has been updated from L483Y, as originally published, to L504Y.

The Rosa26-stopflox-GluA2mut knock-in mice harbor a floxed stop cassette followed by two point mutations (L504Y and R845A) of the glutamate receptor, ionotropic, AMPA2 (alpha 2), gene (Gria2), knocked-into the Gt(ROSA)26Sor locus. These mice may be useful for studying the role of the Gria2 in cre-expressing tissues, specifically as it relates to neurodevelopmental disorders and neurodegenerative diseases.

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