dnPAK transgenic mice have a mouse Camk2a promoter directing postnatal forebrain expression of the mouse dominant negative autoinhibitory domain (AID) of the p21 protein (Cdc42/Rac)-activated kinase (Pak) gene. These mice may be useful for studying the causes of mental retardation, fragile X syndrome, autism, the regulation of synaptic structure and strength, and dendritic spine morphogenesis.
Dr. Susumu Tonegawa, Massachusetts Institute of TechnologyRead More +
dnPAK transgenic mice have a mouse calcium/calmodulin-dependent protein kinase II alpha (Camk2a) promoter directing postnatal forebrain expression of the mouse dominant negative (dn) autoinhibitory domain (AID) of p21 protein (Cdc42/Rac)-activated kinase (Pak) gene (dnPAK). The AID is conserved in all three Pak genes (Pak1, Pak2, Pak3). Homozygous dnPAK mice are viable, fertile, and normal in size. Pak genes are expressed in multiple brain regions, including the cortex and hippocampus, and are critical regulators of actin remodeling. The activation of PAK catalytic activity requires the release of the catalytic domain from the AID and autophosphorylation of a gene specific threonine residue. dnPAK binds to the catalytic domain of PAK and blocks autophosphorylation, inhibiting activation of catalytic activity. dnPAK overexpression causes a decrease in the number of and increase is the size of cortical neuron dendritic spines. Also observed is an increase in the proportion of larger synapses. These cortical neurons exhibit impaired bidirectional modifiability of synaptic strength with enhanced long-term potentiation (LTP) and reduced long-term depression (LTD), leading to a deficit in consolidation and retention of spacial memory. These mice may be useful for studying the regulation of synaptic structure and strength, and dendritic spine morphogenesis associated with the causes of mental retardation, fragile X syndrome, and autism.
The dnPAK transgene was designed with the mouse autoinhibitory domain (AID) of the p21 protein (Cdc42/Rac)-activated kinase (Pak) gene driven by a mouse calcium/calmodulin-dependent protein kinase II alpha (Camk2a) promoter, followed by a simian virus 40 (SV40) polyadenylation site. The transgene was microinjected into fertilized C57BL/6 oocytes and mice from founder line 21 were bred to C57BL/6 mice. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.
|Expressed Gene||Pak3, p21 protein (Cdc42/Rac)-activated kinase 3, mouse, laboratory|
|Site of Expression|
|Allele Name||transgene insertion 21, Susumu Tonegawa|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Gene Symbol and Name||Tg(Camk2a-AIDPak)21Stl, transgene insertion 21, Susumu Tonegawa|
|Promoter||Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory|
|Expressed Gene||Pak3, p21 protein (Cdc42/Rac)-activated kinase 3, mouse, laboratory|
|Strain of Origin||C57BL/6|
|Molecular Note||The dnPAK transgene was designed with the mouse autoinhibitory domain (AID) of the p21 protein (Cdc42/Rac)-activated kinase 3 (Pak3) gene tagged with myc and driven by a mouse calcium/calmodulin-dependent protein kinase II alpha (Camk2a) promoter, followed by a simian virus 40 (SV40) polyadenylation site. This domain is conserved in all three Pak genes (Pak1, Pak2, Pak3). Lines 21 and 110 were generated.|
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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