ABSTRACT
The anterior part of the tongue was examined in wild type and dystonia musculorum mice to assess the effect of dystonin loss on fungiform papillae. In the mutant mouse, the density of fungiform papillae and their taste buds was severely decreased when compared to wild type littermates (papilla, 67% reduction; taste bud, 77% reduction). The mutation also reduced the size of these papillae (17% reduction) and taste buds (29% reduction). In addition, immunohistochemical analysis demonstrated that the dystonin mutation reduced the number of PGP 9.5 and calbindin D28k-containing nerve fibers in fungiform papillae. These data together suggest that dystonin is required for the innervation and development of fungiform papillae and taste buds.
Subject(s)
Carrier Proteins/genetics , Cytoskeletal Proteins/genetics , Nerve Tissue Proteins/genetics , Taste Buds/abnormalities , Taste Buds/metabolism , Taste Disorders/metabolism , Tongue/abnormalities , Tongue/metabolism , Animals , Calbindin 1 , Calbindins , Chorda Tympani Nerve/abnormalities , Chorda Tympani Nerve/metabolism , Chorda Tympani Nerve/physiopathology , Disease Models, Animal , Dystonic Disorders/genetics , Dystonic Disorders/metabolism , Dystonic Disorders/physiopathology , Dystonin , Geniculate Ganglion/abnormalities , Geniculate Ganglion/metabolism , Geniculate Ganglion/physiopathology , Immunohistochemistry , Mice , Mice, Knockout , Mutation/genetics , S100 Calcium Binding Protein G/metabolism , Sensory Receptor Cells/abnormalities , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/physiopathology , Taste Buds/physiopathology , Taste Disorders/genetics , Taste Disorders/physiopathology , Tongue/physiopathology , Ubiquitin Thiolesterase/metabolismABSTRACT
The vagal and glossopharyngeal sensory ganglia and their peripheral tissues were examined in wild type and dystonia musculorum mice to assess the effect of dystonin loss of function on chemoreceptive neurons. In the mutant mouse, the number of vagal and glossopharyngeal sensory neurons was severely decreased (70% reduction) when compared with wild type littermates. The mutation also reduced the size of the circumvallate papilla (45% reduction) and the number of taste buds (89% reduction). In addition, immunohistochemical analysis demonstrated that the dystonin mutation reduced the number of PGP 9.5-, calcitonin gene-related peptide-, P2X3 receptor- and tyrosine hydroxylase-containing neurons. Their peripheral endings also decreased in the taste bud and epithelium of circumvallate papillae. These data together suggest that the survival of vagal and glossopharyngeal sensory neurons is dependent upon dystonin.
Subject(s)
Carrier Proteins/physiology , Cytoskeletal Proteins/physiology , Ganglia, Sensory/abnormalities , Glossopharyngeal Nerve/abnormalities , Nerve Tissue Proteins/physiology , Neurons, Afferent/metabolism , Vagus Nerve/abnormalities , Animals , Animals, Newborn , Calcitonin Gene-Related Peptide/metabolism , Carrier Proteins/genetics , Cell Differentiation/genetics , Cell Survival/genetics , Chemoreceptor Cells/abnormalities , Chemoreceptor Cells/metabolism , Chemoreceptor Cells/pathology , Cytoskeletal Proteins/genetics , Down-Regulation/genetics , Dystonin , Ganglia, Sensory/metabolism , Ganglia, Sensory/pathology , Glossopharyngeal Nerve/metabolism , Glossopharyngeal Nerve/pathology , Mice , Mice, Transgenic , Nerve Tissue Proteins/genetics , Neurons, Afferent/pathology , Nodose Ganglion/abnormalities , Nodose Ganglion/metabolism , Nodose Ganglion/pathology , Receptors, Purinergic P2/metabolism , Receptors, Purinergic P2X3 , Sensory Receptor Cells/abnormalities , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/pathology , Taste/genetics , Taste Buds/abnormalities , Taste Buds/pathology , Tyrosine 3-Monooxygenase/metabolism , Ubiquitin Thiolesterase/metabolism , Vagus Nerve/metabolism , Vagus Nerve/pathologyABSTRACT
Mice lacking a functional NGF gene (ngf-/- mice) have less than one third of the normal complement of sensory neurons, few sympathetic postganglionic neurons and die shortly after birth. We report here that transgenic expression of NGF under control of the K14 keratin promoter can rescue some elements of the peripheral nervous system and restore normal growth and viability to ngf-/- mice. While hybrid transgenic-ngf-/- mice (ngfTKOs) displayed marginal rescue of trigeminal ganglion neurons, the percentage of CGRP-positive neurons was restored to normal. Restoration of CGRP-positive terminals in skin and spinal cord was also found and accompanied by recovery of behavioral responses to noxious stimuli. ngfTKO mice displayed a normal number of superior cervical ganglion neurons and recovery of sympathetic innervation of skin. These results demonstrate that substitution of a functional NGF locus by a transgene directing expression largely to skin can result in normal growth and viability. Thus, the most vital functions of NGF are not dependent on faithful recapitulation of the normal spatiotemporal pattern of gene expression.
Subject(s)
Nerve Growth Factor/deficiency , Neurons, Afferent/metabolism , Peripheral Nervous System/abnormalities , Skin Abnormalities/genetics , Skin/growth & development , Sympathetic Fibers, Postganglionic/abnormalities , Animals , Cell Survival/genetics , Female , Ganglia, Sympathetic/abnormalities , Ganglia, Sympathetic/cytology , Ganglia, Sympathetic/growth & development , Gene Expression Regulation, Developmental/genetics , Genetic Therapy/methods , Male , Mice , Mice, Knockout , Mice, Transgenic , Nerve Growth Factor/biosynthesis , Nerve Growth Factor/genetics , Neurons, Afferent/cytology , Nociceptors/abnormalities , Nociceptors/cytology , Nociceptors/growth & development , Pain/genetics , Pain/metabolism , Peripheral Nervous System/cytology , Peripheral Nervous System/growth & development , Sensory Receptor Cells/abnormalities , Sensory Receptor Cells/cytology , Sensory Receptor Cells/growth & development , Skin/innervation , Skin/metabolism , Skin Abnormalities/metabolism , Sympathetic Fibers, Postganglionic/cytology , Sympathetic Fibers, Postganglionic/growth & development , Transgenes/genetics , Trigeminal Ganglion/abnormalities , Trigeminal Ganglion/cytology , Trigeminal Ganglion/growth & developmentABSTRACT
Retinoic acid (RA) is an active metabolite of vitamin A that is teratogenic when present in excess during mammalian embryogenesis. We have investigated the effect of embryonic exposure to nonphysiological levels of all-trans RA on the development of the mouse inner ear. Dysmorphogenesis of both vestibular and auditory portions of the inner ear, and abnormal formation of the surrounding capsule are produced by exposure to teratogenic levels of RA at an embryonic age of 9 days (E9). There was no observable teratogenic effect of RA when administered at earlier (i.e., E7 or E8) or later (i.e., E10) stages of otic morphogenesis. We hypothesize that exposure to high levels of RA during a critical period of early otic morphogenesis interferes with the inductive tissue interactions required for inner ear development.