Dataset Information

Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome.

ABSTRACT: We asked whether the physiological and morphologic properties of hypoglossal motor neurons (CNXII MNs) that innervate protruder or retractor tongue muscles are disrupted in neonatal LgDel mice that carry a heterozygous deletion parallel to that associated with DiGeorge/22q11.2 deletion syndrome (22q11.2DS). Disrupted coordination of tongue movement in LgDel mouse pups may contribute to suckling, feeding, and swallowing (S/F/S) disruptions that parallel pediatric dysphagia in infants and toddlers with 22q11.2DS. Using an in vitro rhythmically active medullary slice preparation, we found spontaneous firing as well as IPSC frequency differed significantly in neonatal LgDel versus wild-type (WT) protruder and retractor CNXII MNs that were identified by retrograde tracing from their target muscles. In response to respiration-related activity, initiation and decay of transiently increased firing in WT protruder MNs is delayed in LgDel, accompanied by altered excitatory/inhibitory (E/I) balance. In addition, LgDel retractor MNs have a transient increase in firing with diminished IPSC frequency that is not seen in WT. There were no significant differences in cell body volume of either XII class in WT and LgDel Sholl analysis showed the total numbers of dendritic intersections (at 50- and 90-?m radii from the cell soma) were significantly greater for LgDel versus WT retractor MNs. Thus, the physiological, synaptic and cellular properties of distinct classes of CNXII MNs that coordinate tongue movement in neonatal WT mice are altered in LgDel Such changes could contribute to sub-optimal coordination of S/F/S that underlies pediatric dysphagia in 22q11.2DS.

SUBMITTER: Wang X

PROVIDER: S-EPMC7548433 | biostudies-literature | 2020 Sep/Oct

REPOSITORIES: biostudies-literature

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Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome.

Wang Xin X Popratiloff Anastas A Motahari Zahra Z LaMantia Anthony-Samuel AS Mendelowitz David D

eNeuro 20200901 5

We asked whether the physiological and morphologic properties of hypoglossal motor neurons (CNXII MNs) that innervate protruder or retractor tongue muscles are disrupted in neonatal <i>LgDel</i> mice that carry a heterozygous deletion parallel to that associated with DiGeorge/22q11.2 deletion syndrome (22q11.2DS). Disrupted coordination of tongue movement in <i>LgDel</i> mouse pups may contribute to suckling, feeding, and swallowing (S/F/S) disruptions that parallel pediatric dysphagia in infant ...[more]

PMID: 32855199

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Project description:Hemizygous deletions of the chromosome 22q11.2 region result in the 22q11.2 deletion syndrome also referred to as DiGeorge, Velocardiofacial or Shprintzen syndromes. The phenotype is variable but commonly includes conotruncal cardiac defects, palatal abnormalities, learning and behavioral problems, immune deficiency, and facial anomalies. Four distinct highly homologous blocks of low copy number repeat sequences (LCRs) flank the deletion region. Mispairing of LCRs during meiosis with unequal meiotic exchange is assumed to cause the recurrent and consistent deletions. The proximal LCR is reportedly located at 22q11.2 from 17.037 to 17.083 Mb while the distal LCR is located from 19.835 to 19.880 Mb. Although the chromosome breakpoints are thought to localize to the LCRs, the positions of the breakpoints have been investigated in only a few individuals. Therefore, we used high resolution oligonucleotide-based 244K microarray comparative genomic hybridization (aCGH) to resolve the breakpoints in a cohort of 20 subjects with known 22q11.2 deletions. We also investigated copy number variation (CNV) in the rest of the genome. The 22q11.2 breaks occurred on either side of the LCR in our subjects, although more commonly on the distal side of the reported proximal LCR. The proximal breakpoints in our subjects spanned the region from 17.036 to 17.398 Mb. This region includes the genes DGCR6 (DiGeorge syndrome critical region protein 6) and PRODH (proline dehydrogenase 1), along with three open reading frames that may encode proteins of unknown function. The distal breakpoints spanned the region from 19.788 to 20.122 Mb. This region includes the genes GGT2 (gamma-glutamyltransferase-like protein 2), HIC2 (hypermethylated in cancer 2), and multiple transcripts of unknown function. The genes in these two breakpoint regions are variably hemizygous depending on the location of the breakpoints. Our 20 subjects had 254 CNVs throughout the genome, 94 duplications and 160 deletions, ranging in size from 1 kb to 2.4 Mb. The presence or absence of genes at the breakpoints depending on the size of the deletion plus variation in the rest of the genome due to CNVs likely contribute to the variable phenotype associated with the 22q11.2 deletion or DiGeorge syndrome.

Dataset Information

Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome.

Publications

Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome.

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