Rnx deficiency results in congenital central hypoventilation

Senji Shirasawa, Akiko Arata, Hiroshi Onimaru, Kevin A. Roth, Gary A. Brown, Susan Horning, Satoru Arata, Koji Okumura, Takehiko Sasazuki, Stanley J. Korsmeyer

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)


The genes Tlx 1 (Hox11), Enx (Hox11L1, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx-deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx(-/-) mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

Original languageEnglish
Pages (from-to)287-290
Number of pages4
JournalNature genetics
Issue number3
Publication statusPublished - Mar 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics


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