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SP<\/jats:styled-content>\u2010D<\/jats:styled-content> knockout mice show accumulations of foamy alveolar macrophages, alveolar lipoproteinosis and pulmonary emphysema. Three single nucleotide polymorphisms (SNP<\/jats:styled-content>s) have been described in the coding sequence of the human SP<\/jats:styled-content>\u2010D<\/jats:styled-content> gene SFTPD<\/jats:styled-content><\/jats:italic>. Clinical studies showed that the SNP <\/jats:styled-content>SFTPD<\/jats:styled-content><\/jats:italic> with a nucleotide change from A<\/jats:styled-content> to C<\/jats:styled-content> resulting in a M<\/jats:styled-content>et to T<\/jats:styled-content>hr substitution at position 11 in the protein (M<\/jats:styled-content>et(11)T<\/jats:styled-content>hr), is relevant. This study set out to create a humanised mouse model of the M<\/jats:styled-content>et(11)T<\/jats:styled-content>hr SNP<\/jats:styled-content>. Transgenic mice lines expressing either M<\/jats:styled-content>et(11) or T<\/jats:styled-content>hr(11) SP<\/jats:styled-content>\u2010D<\/jats:styled-content> under the control of the ubiquitously expressed pROSA<\/jats:styled-content>26 promoter in C<\/jats:styled-content>57B<\/jats:styled-content>l\/6 SP<\/jats:styled-content>\u2010D<\/jats:styled-content> deficient mice (DKO<\/jats:styled-content>) was created. Both M<\/jats:styled-content>et(11) (142\u00a0\u00b1\u00a052\u00a0ng\u00a0mL\u22121<\/jats:sup>) and T<\/jats:styled-content>hr(11) (228\u00a0\u00b1\u00a076\u00a0ng\u00a0mL\u22121<\/jats:sup>) mice lines expressed human SP<\/jats:styled-content>\u2010D<\/jats:styled-content> at almost similar levels. According to the literature this was within the range of SP<\/jats:styled-content>\u2010D<\/jats:styled-content> levels found in wildtype (WT<\/jats:styled-content>) mice (253\u00a0\u00b1\u00a022\u00a0ng\u00a0mL\u22121<\/jats:sup>). Met(11) or T<\/jats:styled-content>hr(11) SP<\/jats:styled-content>\u2010D<\/jats:styled-content> in serum from transgenic mice bound maltose in a calcium\u2010dependent manner, and binding was inhibited in the presence of EDTA<\/jats:styled-content> or maltose. Bronchoalveolar lavage showed for both transgenic mice lines complementation of the DKO<\/jats:styled-content> phenotype by restoring cell counts, phospholipid levels and protein content back to WT<\/jats:styled-content> levels. Cytospins of BAL<\/jats:styled-content> pellet cells showed a resemblance to WT<\/jats:styled-content> but both mice lines showed some foamy alveolar macrophages. The stereological analysis showed for none of the mice lines a complete abrogation of emphysematous alterations. However, both M<\/jats:styled-content>et(11) and T<\/jats:styled-content>hr(11) mice lines were partially reverted back to a WT<\/jats:styled-content> phenotype when compared with DKO<\/jats:styled-content> mice, indicating important effects on surfactant metabolism in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/joa.12120","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T21:54:53Z","timestamp":1381528493000},"page":"581-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Surfactant protein D<\/scp> (SP<\/scp>\u2010D<\/scp>) deficiency is attenuated in humanised mice expressing the M<\/scp>et(11)T<\/scp>hr short nucleotide polymorphism of SP<\/scp>\u2010D<\/scp>: implications for surfactant metabolism in the lung"],"prefix":"10.1111","volume":"223","author":[{"given":"Lars","family":"Knudsen","sequence":"first","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) Member of the German Center for Lung Research Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Ochs","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boxler","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Tornoe","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Center University of Southern Denmark Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grith","family":"Lykke\u2010Sorensen","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Center University of Southern Denmark Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose\u2010Marie","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Child Health Sir Henry Wellcome Laboratories Academic Unit for Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard W.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Child Health Sir Henry Wellcome Laboratories Academic Unit for Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton UK"},{"name":"Institute for Life Sciences University of Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uffe","family":"Holmskov","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Center University of Southern Denmark Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ochs","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) Member of the German Center for Lung Research Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Child Health Sir Henry Wellcome Laboratories Academic Unit for Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton UK"},{"name":"Institute for Life Sciences University of Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540205000713"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.4049\/jimmunol.161.9.4599","article-title":"Recombinant rat surfactant\u2010associated protein D inhibits human T lymphocyte proliferation and IL\u20102 production","volume":"161","author":"Borron PJ","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11869"},{"key":"e_1_2_9_5_1","first-page":"241","article-title":"Accumulation of surfactant protein D in human pulmonary alveolar proteinosis","volume":"142","author":"Crouch E","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1016\/S0021-9258(18)53869-2","article-title":"Genomic organization of human surfactant protein D (SP\u2010D). 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