Leucine Rich Repeats and Calponin Homology Containing Protein 4 (Lrch4)-deficient Mouse

Leucine rich repeats and calponin homology containing protein 4 (Lrch4) is a gene that encodes a protein predicted to have a C-terminal transmembrane domain, a calponin homology domain, and 5-8 leucine rich repeats (LRRs). We silenced Lrch4 in RAW 264.7 macrophages as well as CD14-MD2-TLR4-HEK293 cells and found that Lrch4 knockdown attenuates responsiveness of cells to LPS and other pathogen-associated molecules. These findings suggest that Lrch4 is a regulator of the innate immune response. In order to facilitate more physiologic in vivo investigations of the function and disease-relevant roles of Lrch4, we produced a Lrch4 ene-deleted mouse. The Lrch4-null mouse will be tested in a wide array of pro-inflammatory and host defense model exposures. In addition, given that our mouse has a floxed Lrch4 allele and that Lrch4 expression is fairly ubiquitous, future tissue-specific Lrch4-deficient murine strains can be generated (e.g., myeloid-specific [LysM-Cre], intestinal epithelial-specific [Villin-Cre], liverspecific [Alb-Crej,etc.). In addition, we have a Lrch4 mouse line with a B-galactosidase construct in the Lrch4 locus Lrch4 Tn1/+, which can be used for expression profiling of Lrch4.