Appl1 Knockout Mouse
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The adaptor protein APPL1 (Adaptor protein containing pleckstrin homology [PH], phosphotyrosine binding [PTB], and Leucine zipper motifs) was first identified as a binding protein of AKT2 and subsequently found to bind to several membrane-bound receptors implicated in the AKT and/or MAPK signal transduction pathways. To clarify the physiologic role of APPL, Drs. Joseph Testa Yinfei Tan, and Huihong You have generated and characterized an Appl1 knockout mouse.
They have reported that mice with complete loss of Appl1 were viable, with no visible abnormality observed. Pups at different postnatal stages thrived and developed normally, with no difference in gross body weight compared to wild-type littermates. Furthermore, 3-month-old mice with each of the three genotypes (-/-, -/+, +/+) had similar organ weights reproductive function also did not appear to be affected. To assess the effect of Appl1 loss on the hematopoietic system, peripheral blood was analyzed and no obvious defect was found in blood from Appl1-null mice.
To evaluate the in vivo role of Appl1 on Akt stability and activation, various adult mouse tissues from wild-type, Appl1+/-, and Appl1-/- mice were subjected to immunoblotting. Loss of Appl1 does not have an obvious effect on serum-, EGF- and insulin-induced Akt activation in Appl1-/- murine embryonic fibroblasts; however, Appl1-/- cells do have compromised Akt activation upon HGF stimulation.
Appl1 knock-out mice are useful for
- Research: on basic mechanisms of Appl1 involvement in pathways mediated by key signaling molecules such as AKT, Rab5, AMPK, etc.
Publications:Yinfei Tan, et al., "Appl1 is Dispensable for Mouse Development, and Loss of Appl1 has Growth Factor- Selective Effects on Akt Signaling in Murine Embryonic Fibroblasts, " J. Biol. Chem. (Dec. 29, 2009)
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