The kringle containing transmembrane protein 1 (Kremen1) gene encodes a high-affinity transmembrane receptor expressed in patch compartment-associated striatal spiny projection neurons (SPNs) in the dorsal striatum, a brain region critical for motor learning, decision-making, and regulation of voluntary movement. In addition to SPNs, Kremen1 is also expressed in subsets of hippocampal neurons and pericytes in the brain. SPNs are broadly classified into two main subtypes: dopamine receptor D1 (Drd1)-expressing direct-pathway neurons (dSPNs) and the dopamine receptor D2 (Drd2)-expressing indirect-pathway SPNs (iSPNs). dSPNs facilitate movement initiation while the iSPNs restrain unwanted movements. SPNs are further subdivided into two distinct compartments within the dorsal striatum: the patch (or striosome) and matrix compartments, identified by specific neurochemical markers and unique input-output connectivity. Notably, activation of patch dSPN can inhibit dopamine release through presynaptic inhibition of dopaminergic neurons (DANs), which leading to locomotor suppression. Kremen12A-Cre knock-in mice were engineered with a 2A-iCre sequence inserted into exon 9, immediately after the stop codon of the Kremen1 gene. This design enables co-expression of Kremen1 and codon improved Cre (iCre) recombinase under the transcriptional regulation of Kremen1. Homozygous Kremen12A-Cre mice are viable and fertile. When crossed with mice containing loxP-flanked sequence, iCre-mediated recombination will result in deletion of the loxP-flanked sequences in patch-associated SPNs of the dorsal striatum. These mice are useful as a tool for studying the anatomy and functional role of patch SPNs in behavioral regulation and neurological disease.

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Kremen12A-Cre knock-in mice are designed to have 2A-iCre sequence inserted into exon 9, immediately after the stop codon of the Kremen1 gene. The endogenous Kremen1 promoter directs expression of codon improved Cre (iCre) recombinase to patch-associated striatal spiny projection neurons (SPNs) in the dorsal striatum (dSPN).These mice are useful as a tool for studying the anatomy and functional role of patch SPNs in behavioral regulation and neurological disease.

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