A mouse with bad hair and poor taste

Abstract

The tufted (tf) locus causes mice of the BTBR strain to lose hair in characteristic waves that spread from snout to tail. These mice are also indifferent to sweeteners, bitter compounds and calcium solutions. To positionally clone the underlying genes, we produced BTBR × NZW/LacJ F2 mice, phenotyped them with a series of taste preference tests, and conducted a genome scan. Preferences for several taste compounds were strongly linked to chromosome 17. To isolate this linkage we developed a congenic line by repeatedly backcrossing chromosome 17 BTBR.NZW mice to the BTBR strain. After 11 backcrosses, the congenic interval involved a 0.8-Mb region containing 21 genes. Tufted hair was present in mice that inherited the BTBR.BTBR haplotype but not the BTBR.NZW haplotype, implying that one of the 21 genes is responsible for the hair loss. A strong candidate to mediate taste deficits was Itpr3, the inositol triphosphate receptor type 3, which is a component of the taste transduction cascade. To evaluate this, we produced Itpr3 knockout mice and used complementation mapping to show that the BTBR form of Itpr3 is nonfunctional. Like the BTBR inbred and BTBR. BTBR congenic control mice, Itpr3 knockout mice were insensitive to sweet, bitter, calcium and other tastes mediated by G protein-coupled receptors. Sequencing the BTBR form of Itpr3 revealed a 12-bp deletion in exon 23, which probably causes the loss of function. Thus, the BTBR mouse has a defective Itpr3 gene to blame for both its bad hair and its poor taste perception.