Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11) deletion syndrome
| Autor: | Beverly A. Karpinski, Anthony-Samuel LaMantia, Samar Nuwayhid, Irene E. Zohn, Matthew S. Fralish, Sally A. Moody, Thomas M. Maynard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Retinoic acid Gene Dosage Medicine (miscellaneous) lcsh:Medicine Cranial nerve development Craniofacial Abnormalities chemistry.chemical_compound Mice 0302 clinical medicine Immunology and Microbiology (miscellaneous) DiGeorge syndrome 0303 health sciences Cranial nerves Cranial Nerves Gene Expression Regulation Developmental Dysphagia Phenotype DiGeorge Female medicine.symptom Chromosome Deletion lcsh:RB1-214 Research Article Signal Transduction TBX1 medicine.medical_specialty Neuroscience (miscellaneous) Hindbrain Tretinoin Biology Gene dosage General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 22q11 Deletion Syndrome 030225 pediatrics Internal medicine Hindbrain patterning medicine lcsh:Pathology DiGeorge Syndrome Animals 030304 developmental biology Body Patterning 22q11 deletion syndrome lcsh:R Feeding Behavior medicine.disease Embryo Mammalian Deglutition Rhombencephalon Disease Models Animal Endocrinology chemistry Animals Newborn Deglutition Disorders T-Box Domain Proteins |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 7, Iss 2, Pp 245-257 (2014) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | SummaryWe assessed feeding-related developmental anomalies in the LgDel mouse model of Chromosome 22q11 Deletion Syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia - debilitating feeding, swallowing and nutrition difficulties from birth onward - within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA) signaling prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal (IX), or vagus (X) cranial nerves (CN) that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to that in wild type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and cranial nerve development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS. |
| Databáze: | OpenAIRE |
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