Abstract
Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dIL(A), and dIL(B) subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dIL(B) cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKCγ-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Newborn
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Capsaicin / toxicity
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Cell Count
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Chloroquine / toxicity
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Embryo, Mammalian
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Ganglia, Spinal / cytology*
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Gastrin-Releasing Peptide / genetics
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Gastrin-Releasing Peptide / metabolism
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Homeodomain Proteins / genetics
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Mice
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Mice, Transgenic
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Muscle Proteins / genetics
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Neurons / classification*
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Neurons / physiology*
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Oligopeptides / toxicity
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Pain / chemically induced
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Pain / genetics
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Pain / metabolism
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Physical Stimulation / adverse effects
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Protein Kinase C / metabolism
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Protein Precursors / genetics
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Protein Precursors / metabolism
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Pruritus / etiology
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Pruritus / metabolism
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Psychomotor Performance / drug effects
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Psychomotor Performance / physiology
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Sensation / genetics*
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Somatostatin / genetics
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Somatostatin / metabolism
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Tachykinins / genetics
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Tachykinins / metabolism
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Vesicular Glutamate Transport Protein 1 / metabolism
Substances
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Homeodomain Proteins
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Lbx1h protein, mouse
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Muscle Proteins
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Oligopeptides
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Protein Precursors
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Slc17a7 protein, mouse
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Tachykinins
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Tlx3 protein, mouse
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Vesicular Glutamate Transport Protein 1
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preprotachykinin
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seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
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Somatostatin
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Gastrin-Releasing Peptide
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Chloroquine
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protein kinase C gamma
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Protein Kinase C
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Capsaicin