{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:49:05Z","timestamp":1792673345299,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,6,9]]},"abstract":"<jats:p>\n                    Pompe disease is a severe form of muscular dystrophy due to glycogen accumulation in all tissues, especially striated muscle. Disease severity is directly related to the deficiency of acid \u03b1-glucosidase (GAA), which degrades glycogen in the lysosome. Respiratory dysfunction is a hallmark of the disease, muscle weakness has been viewed as the underlying cause, and the possibility of an associated neural contribution has not been evaluated previously. Therefore, we examined behavioral and neurophysiological aspects of breathing in 2 animal models of Pompe disease\u2014the\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse and a transgenic line (MTP) expressing GAA only in skeletal muscle, as well as a detailed analysis of the CNS in a Pompe disease patient. Glycogen content was elevated in the\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse cervical spinal cord. Retrograde labeling of phrenic motoneurons showed significantly greater soma size in\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice vs. isogenic controls, and glycogen was observed in\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    phrenic motoneurons. Ventilation, assessed via plethysmography, was attenuated during quiet breathing and hypercapnic challenge in\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice (6 to &gt;21 months of age) vs. controls. We confirmed that MTP mice had normal diaphragmatic contractile properties; however, MTP mice had ventilation similar to the\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice during quiet breathing. Neurophysiological recordings indicated that efferent phrenic nerve inspiratory burst amplitudes were substantially lower in\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and MTP mice vs. controls. In human samples, we demonstrated similar pathology in the cervical spinal cord and greater accumulation of glycogen in spinal cord compared with brain. We conclude that neural output to the diaphragm is deficient in\n                    <jats:italic>Gaa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, and therapies targeting muscle alone may be ineffective in Pompe disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0902534106","type":"journal-article","created":{"date-parts":[[2009,5,27]],"date-time":"2009-05-27T22:14:26Z","timestamp":1243462466000},"page":"9419-9424","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":180,"title":["Neural deficits contribute to respiratory insufficiency in Pompe disease"],"prefix":"10.1073","volume":"106","author":[{"given":"Lara R.","family":"DeRuisseau","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Public Health and Health Professions,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Public Health and Health Professions,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith C.","family":"DeRuisseau","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, College of Health and Human Performance; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"William H.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Departments of dPathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn","family":"Mah","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Therapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Reier","sequence":"additional","affiliation":[{"name":"Neuroscience, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Pediatrics, Molecular Genetics, and Microbiology and Powell Gene Therapy Center, College of Medicine, University of Florida, Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,6,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2003.11.005"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1998"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181815994"},{"key":"e_1_3_3_4_2","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Hirschhorn R","year":"2001","unstructured":"R Hirschhorn, AJJ Reuser, Glycogen storage disease type II; acid \u03b1-glucosidase (acid maltase) deficiency. The Metabolic and Molecular Basis of Inherited Disease, eds CR Scriver, AL Beaudet, WS Sly, D Valle (McGraw-Hill, 8th Ed, New York, Chapter 135. (2001).","edition":"8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0860016"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00808a015"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2008.08.009"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524024605789"},{"key":"e_1_3_3_9_2","first-page":"379","article-title":"Infantile-onset glycogen storage disease type II (Pompe disease): Report of a case with genetic diagnosis and pathological findings","volume":"27","author":"Teng YT","year":"2004","unstructured":"YT Teng, WJ Su, JW Hou, SF Huang, Infantile-onset glycogen storage disease type II (Pompe disease): Report of a case with genetic diagnosis and pathological findings. Chang Gung Med J 27, 379\u2013384 (2004).","journal-title":"Chang Gung Med J"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-196501000-00008"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687878"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-197107000-00008"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.5.906"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000233014.84318.4e"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.19.9.894"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-005-0922-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1722"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.19.2039"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.30.19086"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(92)90779-U"},{"key":"e_1_3_3_21_2","first-page":"R1371","article-title":"Differential control of ventilation among inbred strains of mice","volume":"267","author":"Tankersley CG","year":"1994","unstructured":"CG Tankersley, RS Fitzgerald, SR Kleeberger, Differential control of ventilation among inbred strains of mice. Am J Physiol 267, R1371\u2013R1377 (1994).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80958-7"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1139\/y99-002"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1139\/y99-001"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00215.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01142.2004"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1975.39.4.567"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1965.28.3.560"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02719685"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1993.75.1.63"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90283-H"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-10-04182.2003"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.15.6.715"},{"key":"e_1_3_3_34_2","first-page":"1388","article-title":"Three hypotonic neonates with hypertrophic cardiomyopathy: Pompe's disease","volume":"142","author":"Willemsen MA","year":"1998","unstructured":"MA Willemsen, PE Jira, FJ Gabreels, AT van der Ploeg, JA Smeitink, Three hypotonic neonates with hypertrophic cardiomyopathy: Pompe's disease. Ned Tijdschr Geneeskd 142, 1388\u20131392 (1998).","journal-title":"Ned Tijdschr Geneeskd"},{"key":"e_1_3_3_35_2","first-page":"379","article-title":"Infantile-onset glycogen storage disease type II (Pompe disease): Report of a case with genetic diagnosis and pathological findings","volume":"27","author":"Teng YT","year":"2004","unstructured":"YT Teng, WJ Su, JW Hou, SF Huang, Infantile-onset glycogen storage disease type II (Pompe disease): Report of a case with genetic diagnosis and pathological findings. Chang Gung Med J 27, 379\u2013384 (2004).","journal-title":"Chang Gung Med J"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(50)80174-9"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65361-8"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.8.2196"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.08.022"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.113.5.e448"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20019"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.04.009"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0280-4"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.07.002"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300100"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1970.28.2.234"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(68)90151-9"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-16-07037.1999"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0902534106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:21:53Z","timestamp":1649784113000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0902534106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,9]]},"references-count":48,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2009,6,9]]}},"alternative-id":["10.1073\/pnas.0902534106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0902534106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,9]]},"assertion":[{"value":"2008-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}