Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue

BACKGROUND:The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. METHODS AND FINDINGS:Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1beta, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-beta2, the delta-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as beta-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1beta, PKD2L1, phospholipase C-beta2, and delta-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. CONCLUSIONS:These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals ("natural knockouts") suggests a cell lineage for sour that is independent of the other taste modalities

Genes known to escape X chromosome inactivation predict co-morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure.

Co-morbid chronic musculoskeletal pain (CMSP) and posttraumatic stress symptoms (PTSS) are frequent sequelae of motor vehicle collision, are associated with greater disability than either outcome alone, and are more prevalent in women than men. In the current study we assessed for evidence that gene transcripts originating from the X chromosome contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision. Nested samples were drawn from a longitudinal study of African American individuals, and CMSP (0-10 numeric rating scale) and PTSS (impact of events scale, revised) outcomes were assessed 6 months following motor vehicle collision. Blood RNA were sequenced (n = 101) and the relationship between X chromosome mRNA expression levels and co-morbid CMSP and PTSS outcomes was evaluated using logistic regression analyses. A disproportionate number of peritraumatic X chromosome mRNA predicting CMSP and PTSS in women were genes previously found to escape X chromosome inactivation (11/40, z = -2.9, p = .004). Secondary analyses assessing gene ontology relationships between these genes identified an enrichment in genes known to influence neuronal plasticity. Further, the relationship of expression of two critical regulators of X chromosome inactivation, X-inactive specific transcript (XIST) and Yin Yang 1 (YY1), was different in women developing CMSP and PTSS. Together, these data suggest that X chromosome genes that escape inactivation may contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision