B6N.129-Neto1^tm1Mci/J

Stock number: 021061

Description

These Neto1, neuropilin (NRP) and tolloid (TLL)-like 1, targeted mutation mice exhibit reduced long-term potentiation and deficits in hippocampal-dependent spatial learning. This strain has applications in studies of the N-methyl-D-aspartate (NMDA) receptor complex and synaptic plasticity.

Detailed description

The synaptic membrane protein, neuropilin (NRP) and tolloid (TLL)-like 1, has 2 extracellular CUB domains and a low-density lipoprotein class A (LDLa) domain, and is a component of the synaptic N-methyl-D-aspartate (NMDA) receptor complex. These mice carry a targeted mutation of the Neto1 (Neuropilin (NRP) and tolloid (TLL)-like 1) gene, in which exons 3 through 6 are replaced by a tau-lacZ and floxed NEO cassette. Homozygotes are viable and fertile. No gene product (protein) is detected by immunoblot analysis of brain lysates from homozygotes. Mutant mice that are homozygous for the targeted mutation have fewer NMDA receptors and reduced synaptic kainate receptor currents (kainate receptor mediated excitatory postsynaptic potential) when compared to wildtype mice. Homozygotes exhibit impaired NMDAR (N-methyl-D-aspartate receptor) - dependent spatial learning and memory. The Donating Investigator reports that the beta?galactosidase, lacZ reporter, activity is detected in only a subset of neurons that express Neto1 mRNA. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development

Dr. Roderick R. McInnes, while at University of Toronto, designed a targeting vector, containing a floxed NEO cassette and a tau-lacZ (tlz) cassette, to disrupt exons 2 and 3 of the targeted gene. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animals were crossed to C57BL/6J mice. The mice were then backcrossed to C57BL/6J for 2 generations and then backcrossed to C57BL/6NCrl for more than 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.

Allele

Symbol: Neto1^tm1Mci
Name: targeted mutation 1, Roderick R McInnes
MGI accession ID: MGI:3836584
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Neto1
Marker name: neuropilin (NRP) and tolloid (TLL)-like 1
Chromosome: 18
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: Exon 2 and 3 were replaced with a tau-lacZ (tlz) and floxed neo cassette. The absence of protein expression was confirmed by western blot analysis on brain extracts.