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. 2022 Aug 1;68(4):233-237.
doi: 10.1262/jrd.2022-027. Epub 2022 May 23.

Genetically engineered animal models for Marfan syndrome: challenges associated with the generation of pig models for diseases caused by haploinsufficiency

Naomi Jack  1 , Tomoyuki Muto  2 , Keigo Iemitsu  2 , Tamaki Watanabe  2 , Kazuhiro Umeyama  1 , Jun Ohgane  1   3 , Hiroshi Nagashima  1
Affiliations

Genetically engineered animal models for Marfan syndrome: challenges associated with the generation of pig models for diseases caused by haploinsufficiency

Naomi Jack et al. J Reprod Dev. .

Abstract

Recent developments in reproductive biology have enabled the generation of genetically engineered pigs as models for inherited human diseases. Although a variety of such models for monogenic diseases are currently available, reproduction of human diseases caused by haploinsufficiency remains a major challenge. The present study compares the phenotypes of mouse and pig models of Marfan syndrome (MFS), with a special focus on the expressivity and penetrance of associated symptoms. Furthermore, investigation of the gene regulation mechanisms associated with haploinsufficiency will be of immense utility in developing faithful MFS pig models.

Keywords: Disease model pig; FBN1; Genetic engineering; Haploinsufficiency; Marfan syndrome.

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Conflict of interest statement

There is no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Manifestation of the MFS symptoms in the FBN1mut/+ pig pedigree. Founder FBN1mut/+ cloned pigs (G0; Y256, W198, W226) were generated from nuclear donor cells with genetic background of Large White/Landrace × Duroc. They produced a total of 46 FBN1mut/+ progeny including 3 stillborn offspring (*) over 4 generations. The WT pigs used for mating with the FBN1mut/+ pigs were of the same strain as the nuclear donor cells of Microminipig (MMP, Fuji Micra Inc., Japan). Manifestation of the MFS symptoms in the 43 live pigs were analyzed by laparotomy on day 1 to 1215 postpartum. Squares and circles indicate males and females, respectively. a, Aortic dissection; c, cleft palate; ch, cardiac hypertrophy; d, delayed bone mineralization; e, ectopia lentis; ey, eye abnormalities; f, fragmentation of elastic fibers; hf, heart failure; ip, irregular pulse; j, joint hypermobility; l, lipodystrophy; mv, mitral valve thickening; pc, pectus carinatum; pe, pectus excavatum; s, scoliosis; v, expantion of valsalva cave.
Fig. 2.
Fig. 2.
Variable penetrance of the MFS symptoms in the FBN1mut/+ pig pedigree. Most (81.8%, 9/11) of the manifesting animals displayed the MFS symptoms after 662 days postpartum (a). Solid circles: pigs manifesting symptoms, blank circles: pigs without manifestation.
See this image and copyright information in PMC

References

    1. Hardouin SN, Nagy A. Mouse models for human disease. Clin Genet 2000; 57: 237–244. - PubMed
    1. Rosenthal N, Brown S. The mouse ascending: perspectives for human-disease models. Nat Cell Biol 2007; 9: 993–999. - PubMed
    1. Perlman RL. Mouse models of human disease: An evolutionary perspective. Evol Med Public Health 2016; 2016: 170–176. - PMC - PubMed
    1. Perleberg C, Kind A, Schnieke A. Genetically engineered pigs as models for human disease. Dis Model Mech 2018; 11: dmm030783. - PMC - PubMed
    1. Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Hanfland RA, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB, Jr, Zabner J, Prather RS, Welsh MJ. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 2008; 321: 1837–1841. - PMC - PubMed