The Pacs1 (phosphofurin acidic cluster sorting protein 1) gene encodes a trans-Golgi-membrane traffic regulator that directs protein cargo and is upregulated during embryonic brain development with low expression after birth. A human missense mutation in PACS1, R203W, is associated with developmental delay and intellectual disability (PACS1 syndrome). Functionally, the mutation results in increased dendrite arborization, diminished spine density, and fewer functional synapses. LSL-huPacs1-exon4 R201W conditional knock-in mice carry a CRISPR/Cas9 generated insertion of a humanized exon 4 with the R201W amino acid substitution preceded by a lox-STOP-lox (LSL) cassette in the Pacs1 gene. The mutation is orthologous to the human R203W mutation. The LSL cassette prevents expression of Pacs1 until the cassette is removed by cre-mediated recombination of the loxP sites. Upon recombination, normal transcription resumes into the humanized exon 4 with R201W disease variant. Prior to recombination, homozygous mice are born below expected Mendelian ratios (11.7% of the expected 25% in het x het crosses) but appear healthy and are fertile. mRNA expression of homozygous brain tissue by qRTPCR was unable to detect Pacs1 expression in brain tissue of homozygous LSL mice, with reduced expression in heterozygous mice. When heterozygous LSL males are bred with B6.129S2-Emx1tm1(cre)Krj/J female mice, which express cre in neurons of the neocortex, hippocampus, and glial cells of the pallium, the resulting recombinant mice are born at Mendelian ratios and appear healthy. In recombined mice, mRNA expression of heterozygous brain tissue by qRTPCR showed expression of the humanized exon 4 with the R201W variant.

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LSL-huPacs1-exon4 R201W conditional knock-in mice carry a humanized exon 4 with the R201W amino acid substitution preceded by a lox-STOP-lox (LSL) cassette in the Pacs1
 (phosphofurin acidic cluster sorting protein 1) gene. This strain may 
be useful for research in neurodevelopmental disorders such as PACS1 
syndrome.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.