These Lrp8 knockin mice constitutively express a nonspliceable alternative transcript incorporating exons 17-20 and are useful in studies of neurotransmission.
Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas
Lrp8 (low density lipoprotein receptor-related protein 8; also called Apoer2, apolipoprotein E receptor 2) is a member of the low density lipoprotein (LDL) receptor gene family. In association with its ligand, RELN (reelin), it controls neuronal migration during brain development. It is also essential for induction of long-term potentiation (LTP) in the adult brain. Alternative splicing involving exon 19 controls RELN-mediated modulation of N-methyl-D-aspartate (NMDA) receptor activity, synaptic neurotransmission and memory processes.
In this targeted knock-in strain, a knockin of exons 17-20 of the mouse Lrp8 gene is constitutively expressed from the native promoter to create a model of nonspliceable alternative transcript activity.
Knockin mice that express the knockin exon 19 transcript show robust RELN-dependent increases in LTP induction that are completely abrogated in mice without the exon 19 knockin (see Stock No. 025755). This evidence suggests that exon 19 is required for RELN-enhanced LTP.
Animals expressing the exon 19 transcript show significant increases in NMDA receptor potentials upon RELN perfusion. Animals lacking the exon 19 transcript show no RELN-induced elevation of NMDA receptor-dependent potentials above baseline synaptic responses.
Exons 17-20 of the mouse Lrp8 gene followed by a loxP-flanked neomycin cassette were knocked into/replace the endogenous exon 17 of the gene to create a constitutively-expressed, nonspliceable alternative transcript. The mutation was created through homologous recombination in 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Resultant male chimeric mice were crossed to C57BL/6J females to establish germline transmission. Animals were subsequently bred with germline Meox2-cre animals (see Stock No. 003755) to excise the neomycin cassette. This strain was maintained on a mixed C57BL/6 and 129 genetic background by the donating laboratory.
|Allele Name||targeted mutation 2.1, Joachim Herz|
|Allele Type||Targeted (Modified isoform(s))|
|Allele Synonym(s)||Apoer2[ex19]; Apoer2[long]; ex19|
|Gene Symbol and Name||Lrp8, low density lipoprotein receptor-related protein 8, apolipoprotein e receptor|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A targeting vector containing exons 17-20 and loxP-flanked neomycin cassette encoding the intracellular domain was inserted into the locus such that the locus constitutively expressed the 59 amino acid insert encoded by exon 19. Cre-mediated recombination removed the neomycin cassette.|
Heterozygotes and homozygotes are viable and fertile.
When using the B6;129S-Lrp8tm2.1Her/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022867 in your Materials and Methods section.