{"id":477,"date":"2006-12-09T09:52:47","date_gmt":"2006-12-09T07:52:47","guid":{"rendered":"http:\/\/www.wjst.de\/blog\/2006\/12\/09\/on-mice-and-men-with-asthma\/"},"modified":"2025-03-20T17:14:28","modified_gmt":"2025-03-20T15:14:28","slug":"on-mice-and-men-with-asthma","status":"publish","type":"post","link":"https:\/\/www.wjst.de\/blog\/sciencesurf\/2006\/12\/on-mice-and-men-with-asthma\/","title":{"rendered":"On mice and men with asthma"},"content":{"rendered":"<p>A new series of pro- and con editorials in the <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=17110654&amp;query_hl=3&amp;itool=pubmed_docsum\">Am J Res Crit Care Med<\/a> discusses the question why in some instances mouse models have &#8220;misdirected resources and thinking&#8221;. You may have noticed that I have only rarely used animals for research; the authors of this editorial have collected empirical data on the exploding use of murine models. Despite their attractiveness from a technological point, they are often useless because<\/p>\n<ul>\n<li>mice do not have asthma as even the most hyperresponsive strain does not show spontaneous symptoms<\/li>\n<li>mice do not have allergy &#8211; although sensitization can be manipulated by high intraperitoneal allergen\/adjuvant injection, this does not involve immediate and late airway obstruction.<\/li>\n<li>immune reaction in mice is quite different &#8211; the interfering of some substances like vitamin D cannot be reliable tested, there is no pure Th1 and Th2 reaction in human and less stronger IL-13 response<\/li>\n<li>mice typically can not be challenged with the complex (and interacting) human exposure &#8211; oxidant stress, viral infection, obesity, diet, smoke, pollutants, &#8230;.<\/li>\n<li>time course is difficult to mimicking in the mouse, there is no longterm model<\/li>\n<li>structure of mouse airways is different &#8211; there are fewer airway generations, much less hypertrophy of smooth muscle<\/li>\n<li>inflammation in mouse is parenchymal rather than restricted<\/li>\n<li>humans are outbred, mice are inbred<\/li>\n<li>early microbial environment is different<\/li>\n<li>many promising interventions of mice pathways failed in humans (VLA-4, IL4, IL5, bradykinine, PAF,&#8230;)<\/li>\n<\/ul>\n<p>I am sure there are even more arguments &#8211; I suggest that the authors deserve the <a href=\"http:\/\/www.felix-wankel-forschungspreis.de\/\">Felix-Wankel price<\/a>.<\/p>\n<h3>Addendum<\/h3>\n<p>15 Dec 2006: The <a href=\"http:\/\/www.bmj.com\/cgi\/content\/abstract\/bmj.39048.407928.BEv1?maxtoshow=&amp;HITS=10&amp;hits=10&amp;RESULTFORMAT=&amp;author1=perel&amp;andorexactfulltext=and&amp;searchid=1&amp;FIRSTINDEX=0&amp;sortspec=relevance&amp;resourcetype=HWCIT\">BMJ<\/a> has 6 more examples about the discordance between animal and human studies: steroids in acute head injury, antifibrinolytics in haemorrhage, thrombolysis or tirilazad treatment in acure ischaemic stroke, antenatal steroids to prevent RDS and biphosphonate to treat osteoporosis.<\/p>\n<p>19 Dec 2006: Another <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=17172652&amp;query_hl=1&amp;itool=pubmed_docsum\">pitfall<\/a> paper<\/p>\n<p>31 Dec 2006: A blog on <a href=\"https:\/\/www.wjst.de\/blog\/2006\/12\/31\/3-rs\/\">animal welfare<\/a><\/p>\n<p>25 Apr 2007: Call for better <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=17448336&amp;itool=pubmed_DocSum\">mouse models<\/a><\/p>\n<p>15 Jul 2018: <a href=\"http:\/\/doi.org\/10.4049\/jimmunol.1700453\">Of Mice, Dirty Mice, and Men: Using Mice to Understand Human Immunology<\/a><\/p>\n<p>16 Oct 2019 <a href=\"https:\/\/www.wjst.de\/blog\/sciencesurf\/2019\/10\/allergy-protection-on-farms-why-also-studies-in-mice-could-have-failed\/\">Allergy protection on farms &#8211; why also studies in mice could have failed<\/a><\/p>\n<p>18 Feb 2023 <a href=\"https:\/\/www.newyorker.com\/culture\/annals-of-inquiry\/the-case-for-free-range-lab-mice\">The case for free running lab mice<\/a>, see<br \/>\n<a href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0092-8674(17)31065-6\">Cell<\/a> and <a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.aaw4361\">Science<\/a> paper<\/p>\n<p>7 Jan\u00a0 2023: A review concluding that\u00a0 <a href=\"https:\/\/www.mdpi.com\/2571-841X\/3\/1\/1\">The vitamin D system in humans and mice: Similar but not the same<\/a><\/p>\n<p>12 March 2024: <a href=\"https:\/\/pubpeer.com\/publications\/73EB3180A077941B77D4A064373B88\">Limitations of the mouse model<\/a><\/p>\n<ul>\n<li>Lack of clinical relevance \u2013 The OVA model often fails to accurately replicate human asthma and allergic diseases. OVA is not a common human allergen, unlike house dust mites, pollen, and pet dander.<\/li>\n<li>Artificial sensitization \u2013 The model requires sensitization with alum, a strong Th2-skewing adjuvant, which does not reflect natural allergen exposure in humans.<\/li>\n<li>Simplistic immune response \u2013 OVA exposure leads to a predominantly Th2 immune response, whereas human asthma involves a complex interplay of Th1, Th2, Th17, and innate immune responses.<\/li>\n<li>Limited chronicity \u2013 Most OVA models induce short-term allergic inflammation but fail to reproduce the chronic airway remodeling, fibrosis, and structural changes seen in human asthma.<\/li>\n<li>Non-physiological exposure \u2013 OVA is often administered at high doses via intraperitoneal injection or repeated aerosol exposure, which does not mimic real-life human allergen exposure.<\/li>\n<li>Strain-specific bias \u2013 Different mouse strains respond variably to OVA, making it difficult to generalize findings.<\/li>\n<li>Lack of environmental and genetic factors \u2013 The model does not account for genetic predisposition, pollution, infections, or microbiome variations that influence human allergic disease development.<\/li>\n<li>Poor translational value \u2013 Many drugs that show promise in OVA models fail in human clinical trials, highlighting the model\u2019s limited predictive power.<\/li>\n<\/ul>\n\n<p>&nbsp;<\/p>\n<div class=\"bottom-note\">\n  <span class=\"mod1\">CC-BY-NC Science Surf , accessed 13.04.2026<\/span>\n <\/div>","protected":false},"excerpt":{"rendered":"<p>A new series of pro- and con editorials in the Am J Res Crit Care Med discusses the question why in some instances mouse models have &#8220;misdirected resources and thinking&#8221;. You may have noticed that I have only rarely used animals for research; the authors of this editorial have collected empirical data on the exploding &hellip; <a href=\"https:\/\/www.wjst.de\/blog\/sciencesurf\/2006\/12\/on-mice-and-men-with-asthma\/\" class=\"more-link\">Continue reading <span class=\"screen-reader-text\">On mice and men with asthma<\/span> <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8,2],"tags":[2948,2945,395,83,396,394,397],"class_list":["post-477","post","type-post","status-publish","format-standard","hentry","category-asthma-allergy","category-genetics-biology","tag-asthma-allergy","tag-genetics-biology","tag-airway-generation","tag-asthma","tag-inflammation","tag-mouse-model","tag-outbred"],"_links":{"self":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts\/477","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/comments?post=477"}],"version-history":[{"count":5,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts\/477\/revisions"}],"predecessor-version":[{"id":24904,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts\/477\/revisions\/24904"}],"wp:attachment":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/media?parent=477"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/categories?post=477"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/tags?post=477"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}