BODY LENGTH INFLUENCES MURINE OESOPHAGEAL LENGTH
DOI:
https://doi.org/10.26873/SVR-2339-2026Keywords:
mice, CD-1, oesophagus, length, model, outbredAbstract
Mouse models are frequently used in research of oesophageal carcinoma, one of the most prevalent and deadly cancers of the world. Surgical mouse models have been described in a variety of strains and stocks, but the distinct anatomy has not been evaluated before. This is crucial for the investigation of malignant fistulas to the airways, which primarily occur in the mid-oesophagus and within 20 millimetres to the tracheal bifurcation and severely limit survival. We therefore investigated oesophageal and tracheal lengths and their relationship to age, bodyweight, and body length in Crl:CD1(ICR) mice. Using 177 mice, based on an a-priori power-analysis, we found a mean oesophageal length of 38.9 millimetres (standard deviation 4.8) and a mean tracheal length of 16.1 millimetres (standard deviation 1.9). This resulted in a position of the carina relative to the oesophagus at 42% of the oesophageal length. Only body length had a statistically significant association to oesophageal length (t=9.56, P<0.001) in a multivariable regression with an adjusted R² of 0.53, but not age (t=1.53, P=0.13) or bodyweight (t=1.05, P=0.3). All three parameters age (t=2.87, P=0.005), bodyweight (t=3.02, P=0.003), and body length (t=2.7, P=0.008) were associated to tracheal length, but with a relevantly lower adjusted R² of 0.4. Unlike in rats, where it is in the proximal oesophagus, the tracheal bifurcation is in the mid-oesophagus in mice. The relationship of oesophageal and tracheal length to body length might improve standardisation in surgical mouse models and thereby increase their reproducibility.
References
Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projec-tions to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022;163:649-658.e2. https://doi.org/10.1053/j.gastro.2022.05.054
Qi L, Sun M, Liu W, Zhang X, Yu Y, Tian Z, et al. Global esophageal cancer epidemiology in 2022 and predictions for 2050: A comprehensive analysis and projections based on GLOBOCAN data. Chin Med J. 2024;137:3108–16. https://doi.org/10.1097/CM9.0000000000003420
Mahmoudian RA, Farshchian M, Golyan FF, Mahmoudian P, Alasti A, Mog-himi V, et al. Preclinical tumor mouse models for studying esophageal can-cer. Crit Rev Oncol Hematol. 2023;189:104068. https://doi.org/10.1016/j.critrevonc.2023.104068
Levrat M, Lambert R, Kirshbaum G. Esophagitis produced by reflux of duodenal contents in rats. Digest Dis Sci. 1962;7:564–73. https://doi.org/10.1007/ BF02236137
Kapoor H, Lohani KR, Lee TH, Agrawal DK, Mittal SK. Animal Models of Barrett’s Esophagus and Esophageal Adenocarcinoma-Past, Present, and Future: Animal Models of Barrett’s Carcinogenesis. Clin Transl Sci. 2015;8:841–7. https://doi.org/ 10.1111/cts.12304
Raggi M, Langer R, Feith M, Friess H, Schauer M, Theisen J. Successful evaluation of a new animal model using mice for esophageal adenocarcino-ma. Langenbecks Arch Surg. 2010;395:347–50. https://doi.org/10.1007/s00423-010-0607-4
Aikou S, Aida J, Takubo K, Yamagata Y, Seto Y, Kaminishi M, et al. Columnar metaplasia in a surgical mouse model of gastro-esophageal reflux disease is not derived from bone marrow-derived cell. Cancer Sci. 2013;104:1154–61. https://doi.org/10.1111/cas.12213
Pham TH, Genta RM, Spechler SJ, Souza RF, Wang DH. Development and Characterization of a Surgical Mouse Model of Reflux Esophagitis and Bar-rett’s Esophagus. J Gastrointest Surg. 2014;18:234–41. https://doi.org/10.1007/s11605-013-2386-z
Davelaar AL, Straub D, Buttar NS, Fockens P, Krishnadath KK. Active matrix metalloproteases are expressed early on and are high during the Barrett’s esophagus malignancy sequence. Scand J Gastroenterol. 2015;50:321–32. https://doi.org/10. 3109 / 00365521.2014.940379
Caspa Gokulan R, Paulrasu K, Azfar J, El-Rifai W, Que J, Boutaud OG, et al. Protein adduction causes non-mutational inhibition of p53 tumor suppressor. Cell Rep. 2023;42:112024. https://doi.org/10.1016/j.celrep.2023.112024
Hao J, Liu B, Yang CS, Chen X. Gastroesophageal reflux leads to esophage-al cancer in a surgical model with mice. BMC Gastroenterology. 2009;9:59. https://doi.org/10.1186/1471-230X-9-59
Fein M, Peters JH, Baril N, McGarvey M, Chandrasoma P, Shibata D, et al. Loss of Function ofTrp53, but NotApc, Leads to the Development of Esophageal Adenocarcinoma in Mice with Jejunoesophageal Reflux. J Surg Res. 1999;83:48–55. https://doi.org/10.1006/jsre.1998.5559
Ellis FH, Xu X, Kulke MH, LoCicero J, Loda M. Malignant transformation of the esophageal mucosa is enhanced in p27 knockout mice. J Thorac Cardio-vasc Surg. 2001;122:809–14. https://doi.org/10.1067/mtc.2001.116471
Lechpammer M, Xu X, Ellis FH, Bhattacharaya N, Shapiro GI, Loda M. Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice. Oncogene. 2006;24:1683–8. https://doi.org/10.1038/sj.onc.1208375
Nuber M, Lindner A, Baumgart J, Baumgart N, Heimann A, Schröder A, et al. Sex represents a relevant interaction in Sprague–Dawley rats: the example of oesophageal length*. All Life. 2020;13:448–55. https://doi.org/10.1080/26895293. 2020. 1806118
Shamji FM, Inculet R. Management of Malignant Tracheoesophageal Fistula. Thorac Surg Clin. 2018;28:393–402. https://doi.org/10.1016/j.thorsurg.2018.04. 007
Treuting PM, Snyder JM. Mouse Necropsy. CP Mouse Biology. 2015;5:223–33. https://doi.org/10.1002/9780470942390.mo140296
International Committee on Veterinary Gross Anatomical Nomenclature ICVGAN, editor. Nomina Anatomica Veterinaria (Internet). 6th edn. 2017. https://www.wava-amav.org/downloads/nav_6_2017.zip
Ni Bhraonain EP, Turner JA, Hannigan KI, Sanders KM, Cobine CA. Immu-nohistochemical characterization of interstitial cells and their spatial relati-onship to motor neurons within the mouse esophagus. Cell Tissue Res. 2025;399:61–84. https://doi.org/10.1007/s00441-024-03929-z
Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Bev Res Method. 2007;39:175–91. https://doi.org/10.3758/BF03193146
Ertim B, Akinci E, Von Stumberg M, Katzer D, Ganschow R, Vilz TO, et al. The Resistance to Traction Forces Differs Substantially Between Intestinal Parts, but Not Between In- and Outbred Strains of Mice. Gastroenterol In-sights. 2026;17:12. https://doi.org/10.3390/gastroent17010012
Burt M, Diehl W, Martini N, Bains MS, Ginsberg RJ, McCormack PM, et al. Malignant esophagorespiratory fistula: Management options and survival. Ann Thorac Surg. 1991;52:1222–9. https://doi.org/10.1016/0003-4975(91)90005-B
Balazs A, Kupcsulik PK, Galambos Z. Esophagorespiratory fistulas of tumorous origin. Non-operative management of 264 cases in a 20-year period. Eur J Cardiothorac Surg. 2008;34:1103–7. https://doi.org/10.1016/j.ejcts.2008.06.025
Lindner A, Tagkalos E, Heimann A, Nuber M, Baumgart J, Baumgart N, et al. Tracheal bifurcation located at proximal third of oesophageal length in Sprague Dawley rats of all ages. Scand J Lab Anim Sci. 2020;46:25–30.
He J, Fang Y, Chen X. Surgical Models of Gastroesophageal Reflux with Mice. JoVE. 2015;53012. https://doi.org/10.3791/53012
Gronnier C, Bruyère E, Piessen G, Briez N, Bot J, Buob D, et al. Operatively induced chronic reflux in rats: A suitable model for studying esophageal carcinogenesis? Surgery. 2013;154:955–67. https://doi.org/10.1016/j.surg.2013.05.029
Guan X, Liu C, Zhou T, Ma Z, Zhang C, Wang B, et al. Survival and progno-stic factors of patients with esophageal fistula in advanced esophageal squamous cell carcinoma. Biosci Rep. 2020;40:BSR20193379. https://doi.org/10.1042/BSR2019 3379
Von Stumberg M, Akinci E, Ertim B, Oetzmann Von Sochaczewski C. Shortcoming of the Mouse Model of Postoperative Ileus: Small Intestinal Lengths Have Similar Variations in In- and Outbred Mice and Cannot Be Predicted by Allometric Parameters. Biomedicines. 2025;13:2948. https://doi.org/10.3390/biomedicines13122948
Strobel CT, Byrne WJ, Ament ME, Euler AR. Correlation of esophageal lengths in children with height: Application to the Tuttle test without prior esophageal manometry. J Pediatr. 1979;94:81–4. https://doi.org/10.1016/S0022-3476(79)80361-3
Putnam PE, Orenstein SR. Determining esophageal length from crown-rump length. J Pediatr Gastroenterol Nutr. 1991;13:354–9.
Miller LR, Marks C, Becker JB, Hurn PD, Chen W-J, Woodruff T, et al. Con-sidering sex as a biological variable in preclinical research. FASEB J. 2017;31:29–34. https://doi.org/10.1096/fj.201600781R
Karp NA, Reavey N. Sex bias in preclinical research and an exploration of how to change the status quo. Br J Pharmacol. 2019;176:4107–18. https://doi.org/10. 1111/ bph.14539
Tuttle AH, Philip VM, Chesler EJ, Mogil JS. Comparing phenotypic varia-tion between inbred and outbred mice. Nat Methods. 2018;15:994–6. https://doi.org/10.1038/s41592-018-0224-7
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Maximiliane von Stumberg, Ejder Akinci, Berkan Ertim, Tim O. Vilz, Christina Oetzmann von Sochaczewski*

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.