JC Clark, TE Weaver, HS Iwamoto, M Ikegami, AH Jobe, WM Hull and JA Whitsett
Division of Neonatology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.

Genetic ablation of the murine SP-B gene in transgenic mice caused lethal perinatal respiratory distress in homozygous offspring, whereas heterozygous SP-B (+/-) mice survived postnatally. In adult SP-B(+/-) mice, surfactant protein B mRNA and the alveolar lavage SP-B protein were reduced by 50% compared with wild-type littermates, consistent with the inactivation of a single SP-B allele. Expression of SP-A, SP- C, and SP-D proteins was not affected in SP-B(+/-) mice. Heterozygous SP-B(+/-) mice reached maturity in numbers expected by Mendelian inheritance of a recessive gene. Lung morphology and both intracellular and extracellular phospholipid pool size and composition were unaltered in the SP-B(+/-) mice. Despite normal survival, pulmonary function studies demonstrated a consistent decrease in lung compliance in SP- B(+/-) mice. Abnormalities of inflation/deflation curves demonstrated airway collapse at low deflation pressures. Residual volumes were increased in the SP-B(+/-) mice. In summary, SP-B mRNA and SP-B protein were reduced by 50% in SP-B(+/-) mice, resulting in abnormalities of lung compliance and air trapping, suggesting a potential susceptibility to pulmonary dysfunction associated with SP-B deficiency.

This article has been cited by other articles:

				D. Jain, E. Atochina-Vasserman, H. Kadire, Y. Tomer, A. Inch, P. Scott, R. C. Savani, A. J. Gow, and M. F. Beers SP-D-deficient mice are resistant to hyperoxia Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L861 - L871. [Abstract] [Full Text] [PDF]

				W. K. Steagall, J.-P. Lin, and J. Moss The C/A(-18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L448 - L453. [Abstract] [Full Text] [PDF]

				A. Das and V. Boggaram Proteasome dysfunction inhibits surfactant protein gene expression in lung epithelial cells: mechanism of inhibition of SP-B gene expression Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L74 - L84. [Abstract] [Full Text] [PDF]

				L. Sparkman, H. Chandru, and V. Boggaram Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L351 - L358. [Abstract] [Full Text] [PDF]

				S. C. Wesselkamper, S. A. McDowell, M. Medvedovic, T. P. Dalton, H. S. Deshmukh, M. A. Sartor, L. M. Case, L. N. Henning, M. T. Borchers, C. R. Tomlinson, et al. The Role of Metallothionein in the Pathogenesis of Acute Lung Injury Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 73 - 82. [Abstract] [Full Text] [PDF]

				L. L. Nesslein, K. R. Melton, M. Ikegami, C.-L. Na, S. E. Wert, W. R. Rice, J. A. Whitsett, and T. E. Weaver Partial SP-B deficiency perturbs lung function and causes air space abnormalities Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1154 - L1161. [Abstract] [Full Text] [PDF]

				M. Rova, R. Haataja, R. Marttila, V. Ollikainen, O. Tammela, and M. Hallman Data mining and multiparameter analysis of lung surfactant protein genes in bronchopulmonary dysplasia Hum. Mol. Genet., June 1, 2004; 13(11): 1095 - 1104. [Abstract] [Full Text] [PDF]

				F. Buhling, N. Waldburg, A. Reisenauer, A. Heimburg, H. Golpon, and T. Welte Lysosomal cysteine proteases in the lung: role in protein processing and immunoregulation Eur. Respir. J., April 1, 2004; 23(4): 620 - 628. [Abstract] [Full Text] [PDF]

				M. N. Gong, Z. Wei, L.-L. Xu, D. P. Miller, B. T. Thompson, and D. C. Christiani Polymorphism in the Surfactant Protein-B Gene, Gender, and the Risk of Direct Pulmonary Injury and ARDS Chest, January 1, 2004; 125(1): 203 - 211. [Abstract] [Full Text] [PDF]

				D. Salinas, L. Sparkman, K. Berhane, and V. Boggaram Nitric oxide inhibits surfactant protein B gene expression in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1153 - L1165. [Abstract] [Full Text] [PDF]

				K. R. Melton, L. L. Nesslein, M. Ikegami, J. W. Tichelaar, J. C. Clark, J. A. Whitsett, and T. E. Weaver SP-B deficiency causes respiratory failure in adult mice Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L543 - L549. [Abstract] [Full Text] [PDF]

				R. Epaud, M. Ikegami, J. A. Whitsett, A. H. Jobe, T. E. Weaver, and H. T. Akinbi Surfactant Protein B Inhibits Endotoxin-Induced Lung Inflammation Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 373 - 378. [Abstract] [Full Text] [PDF]

				Z. Wang, J. E. Baatz, B. A. Holm, and R. H. Notter Content-dependent activity of lung surfactant protein B in mixtures with lipids Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L897 - L906. [Abstract] [Full Text] [PDF]

				J. F. Seymour and J. J. Presneill Pulmonary Alveolar Proteinosis: Progress in the First 44 Years Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 215 - 235. [Abstract] [Full Text] [PDF]

				W. D. Hardie, D. R. Prows, A. Piljan-Gentle, M. R. Dunlavy, S. C. Wesselkamper, G. D. Leikauf, and T. R. Korfhagen Dose-Related Protection from Nickel-Induced Lung Injury in Transgenic Mice Expressing Human Transforming Growth Factor-alpha Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 430 - 437. [Abstract] [Full Text] [PDF]

				M. Ikegami, T. E. Weaver, J. J. Conkright, P. D. Sly, G. F. Ross, J. A. Whitsett, and S. W. Glasser Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury J Appl Physiol, February 1, 2002; 92(2): 519 - 526. [Abstract] [Full Text] [PDF]

				X. Guo, H-M. Lin, Z. Lin, M. Montano, R. Sansores, G. Wang, S. DiAngelo, A. Pardo, M. Selman, and J. Floros Surfactant protein gene A, B, and D marker alleles in chronic obstructive pulmonary disease of a Mexican population Eur. Respir. J., September 1, 2001; 18(3): 482 - 490. [Abstract] [Full Text] [PDF]

				K. Berhane, R. K. Margana, and V. Boggaram Characterization of rabbit SP-B promoter region responsive to downregulation by tumor necrosis factor-alpha Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L806 - L814. [Abstract] [Full Text] [PDF]

				V. Glumoff, O. Väyrynen, T. Kangas, and M. Hallman Degree of Lung Maturity Determines the Direction of the Interleukin-1- Induced Effect on the Expression of Surfactant Proteins Am. J. Respir. Cell Mol. Biol., March 1, 2000; 22(3): 280 - 288. [Abstract] [Full Text]

				L. M. NOGEE, S. E. WERT, S. A. PROFFIT, W. M. HULL, and J. A. WHITSETT Allelic Heterogeneity in Hereditary Surfactant Protein B (SP-B) Deficiency Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 973 - 981. [Abstract] [Full Text] [PDF]

				E. N. Atochina, M. F. Beers, S. T. Scanlon, A. M. Preston, and J. M. Beck P. carinii induces selective alterations in component expression and biophysical activity of lung surfactant Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L599 - L609. [Abstract] [Full Text] [PDF]

				F. S. Cole, A. Hamvas, P. Rubinstein, E. King, M. Trusgnich, L. M. Nogee, D. E. deMello, and H. R. Colten Population-Based Estimates of Surfactant Protein B Deficiency Pediatrics, March 1, 2000; 105(3): 538 - 541. [Abstract] [Full Text]

				A. Naltner, M. Ghaffari, J. A. Whitsett, and C. Yan Retinoic Acid Stimulation of the Human Surfactant Protein B Promoter Is Thyroid Transcription Factor 1 Site-dependent J. Biol. Chem., January 7, 2000; 275(1): 56 - 62. [Abstract] [Full Text] [PDF]

				K. Tokieda, H. S. Iwamoto, C. Bachurski, S. E. Wert, W. M. Hull, K. Ikeda, and J. A. Whitsett Surfactant Protein-B-Deficient Mice Are Susceptible to Hyperoxic Lung Injury Am. J. Respir. Cell Mol. Biol., October 1, 1999; 21(4): 463 - 472. [Abstract] [Full Text]

				E. Kerem, T. Bistritzer, A. Hanukoglu, T. Hofmann, Z. Zhou, W. Bennett, E. MacLaughlin, P. Barker, M. Nash, L. Quittell, et al. Pulmonary Epithelial Sodium-Channel Dysfunction and Excess Airway Liquid in Pseudohypoaldosteronism N. Engl. J. Med., July 15, 1999; 341(3): 156 - 162. [Abstract] [Full Text] [PDF]

				S. Lin, C.-L. Na, H. T. Akinbi, K. S. Apsley, J. A. Whitsett, and T. E. Weaver Surfactant Protein B (SP-B) -/- Mice Are Rescued by Restoration of SP-B Expression in Alveolar Type II Cells but Not Clara Cells J. Biol. Chem., July 2, 1999; 274(27): 19168 - 19174. [Abstract] [Full Text] [PDF]

				Z. Sever-Chroneos, C. J. Bachurski, C. Yan, and J. A. Whitsett Regulation of mouse SP-B gene promoter by AP-1 family members Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L79 - L88. [Abstract] [Full Text] [PDF]

				J. M. HOHLFELD, K. AHLF, G. ENHORNING, K. BALKE, V. J. ERPENBECK, J. PETSCHALLIES, H. G. HOYMANN, H. FABEL, and N. KRUG Dysfunction of Pulmonary Surfactant in Asthmatics after Segmental Allergen Challenge Am. J. Respir. Crit. Care Med., June 1, 1999; 159(6): 1803 - 1809. [Abstract] [Full Text]

				E. Matthew, R. Pun, M. Simonich, H. Iwamoto, and J. Dedman Cyclosporin A protects lung function from hyperoxic damage Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L786 - L795. [Abstract] [Full Text] [PDF]

				R. D. YUSEN, A. H. COHEN, and A. HAMVAS Normal Lung Function in Subjects Heterozygous for Surfactant Protein-B Deficiency Am. J. Respir. Crit. Care Med., February 1, 1999; 159(2): 411 - 414. [Abstract] [Full Text]

				C. HERMANS and A. BERNARD Lung Epithelium-specific Proteins . Characteristics and Potential Applications as Markers Am. J. Respir. Crit. Care Med., February 1, 1999; 159(2): 646 - 678. [Full Text]

				S. H. Guttentag, M. F. Beers, B. M. Bieler, and P. L. Ballard Surfactant protein B processing in human fetal lung Am J Physiol Lung Cell Mol Physiol, September 1, 1998; 275(3): L559 - L566. [Abstract] [Full Text] [PDF]

				G. S. Pryhuber, R. Khalak, and Q. Zhao Regulation of surfactant proteins A and B by TNF-alpha and phorbol ester independent of NF-kappa B Am J Physiol Lung Cell Mol Physiol, February 1, 1998; 274(2): L289 - L295. [Abstract] [Full Text] [PDF]

				M. S. Strayer, S. H. Guttentag, and P. L. Ballard Targeting Type II and Clara Cells for Adenovirus-mediated Gene Transfer Using the Surfactant Protein B Promoter Am. J. Respir. Cell Mol. Biol., January 1, 1998; 18(1): 1 - 9. [Abstract] [Full Text]

				M. Ikegami, A. H. Jobe, J. A. H. Reed, and J. A. Whitsett Surfactant metabolic consequences of overexpression of GM-CSF in the epithelium of GM-CSF-deficient mice Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L709 - L714. [Abstract] [Full Text] [PDF]

				K. Tokieda, J. A. Whitsett, J. C. Clark, T. E. Weaver, K. Ikeda, K. B. McConnell, A. H. Jobe, M. Ikegami, and H. S. Iwamoto Pulmonary dysfunction in neonatal SP-B-deficient mice Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L875 - L882. [Abstract] [Full Text] [PDF]

				H. T. Akinbi, J. S. Breslin, M. Ikegami, H. S. Iwamoto, J. C. Clark, J. A. Whitsett, A. H. Jobe, and T. E. Weaver Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein. FUNCTION OF THE C-TERMINAL PROPEPTIDE J. Biol. Chem., April 11, 1997; 272(15): 9640 - 9647. [Abstract] [Full Text] [PDF]

				C. Yan, A. Naltner, J. Conkright, and M. Ghaffari Protein-Protein Interaction of Retinoic Acid Receptor alpha and Thyroid Transcription Factor-1 in Respiratory Epithelial Cells J. Biol. Chem., June 8, 2001; 276(24): 21686 - 21691. [Abstract] [Full Text] [PDF]

				O. Vayrynen, V. Glumoff, and M. Hallman Regulation of surfactant proteins by LPS and proinflammatory cytokines in fetal and newborn lung Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L803 - L810. [Abstract] [Full Text] [PDF]