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Publication : MASH-1/RET pathway involvement in development of brain stem control of respiratory frequency in newborn mice.

First Author  Dauger S Year  2001
Journal  Physiol Genomics Volume  7
Issue  2 Pages  149-57
PubMed ID  11773601 Mgi Jnum  J:124459
Mgi Id  MGI:3721734 Doi  10.1152/physiolgenomics.00056.2001
Citation  Dauger S, et al. (2001) MASH-1/RET pathway involvement in development of brain stem control of respiratory frequency in newborn mice. Physiol Genomics 7(2):149-57
abstractText  Respiratory abnormalities have been described in MASH-1 (mammalian achaete-scute homologous gene) and c-RET ('rearranged during transfection') mutant newborn mice. However, the neural mechanisms underlying these abnormalities have not been studied. We tested the hypothesis that the MASH-1 mutation may impair c-RET expression in brain stem neurons involved in the control of breathing. To do this, we analyzed brain stem c-RET expression and respiratory phenotype in MASH-1 +/+ wild-type, MASH-1 +/- heterozygous, and MASH-1 -/- knock-out newborn mice during the first 2 h of life. In MASH-1 -/- newborns, c-RET gene expression was absent in the noradrenergic nuclei (A2, A5, A6, A7) that contribute to modulate respiratory frequency and in scattered cells of the rostral ventrolateral medulla. The c-RET transcript levels measured by quantitative RT-PCR were lower in MASH-1 -/- and MASH-1 +/- than in MASH-1 +/+ brain stems (P = 0.001 and P = 0.003, respectively). Breath durations were shorter in MASH-1 -/- and MASH-1 +/- than in MASH-1 +/+ mice (P = 0.022) and were weakly correlated with c-RET transcript levels (P = 0.032). Taken together, these results provide evidence that MASH-1 is upstream of c-RET in noradrenergic brain stem neurons important for respiratory rhythm modulation.
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