Approximately 35 % of the mouse genes are indispensable for life, thus, global knock-out (KO) of those genes may result in embryonic or early postnatal lethality due to developmental abnormalities. Several KO mouse lines are valuable human disease models, but viable homozygous mutant mice are frequently required to mirror most symptoms of a human disease. The site-specific gene editing systems, the transcription activator-like effector nucleases (TALENs), Zinc-finger nucleases (ZFNs) and the clustered regularly interspaced short palindrome repeat-associated Cas9 nuclease (CRISPR/Cas9) made the generation of KO mice more efficient than before, but the homozygous lethality is still an undesired side-effect in case of many genes. The literature search was conducted using PubMed and Web of Science databases until June 30th, 2020. The following terms were combined to find relevant studies: "lethality", "mice", "knock-out", "deficient", "embryonic", "perinatal", "rescue". Additional manual search was also performed to find the related human diseases in the Online Mendelian Inheritance in Man (OMIM) database and to check the citations of the selected studies for rescuing methods. In this review, the possible solutions for rescuing human disease-relevant homozygous KO mice lethal phenotypes were summarized.

NARIC Agricultural Biotechnology Institute Animal Biotechnology Department Gödöllő Hungary

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BALAKRISHNAN B, VERHEIJEN J, LUPO A, RAYMOND K, TURGEON C, YANG Y, CARTER KL, WHITEHEAD KJ, KOZICZ T, MORAVA E, LAI K. A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality. J Inherit Metab Dis. 2019;42:998–1007. doi: 10.1002/jimd.12110. PubMed DOI PMC

BALI D, SVETLANOV A, LEE HW, FUSCO-DEMANE D, LEISER M, LI B, BARZILAI N, SURANA M, HOU H, FLEISCHER N, DEPINHO R, ROSSETTI L, EFRAT S. Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. J Biol Chem. 1995;270:21464–21467. doi: 10.1074/jbc.270.37.21464. PubMed DOI

BONNE G, Di BARLETTA MR, VARNOUS S, BECANE HM, HAMMOUDA EH, MERLINI L, MUNTONI F, GREENBERG CR, GARY F, URTIZBEREA JA, DUBOC D, FARDEAU M, TONIOLO D, SCHWARTZ K. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999;21:285–288. doi: 10.1038/6799. PubMed DOI

BROWN SD, MOORE MW. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping. Mamm Genome. 2012;23:632–640. doi: 10.1007/s00335-012-9427-x. PubMed DOI PMC

CAO H, HEGELE RA. LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090) J Hum Genet. 2003;48:271–274. doi: 10.1007/s10038-003-0025-3. PubMed DOI

CEASAR SA, RAJAN V, PRYKHOZHIJ SV, BERMAN JN, IGNACIMUTHU S. Insert, remove or replace: A highly advanced genome editing system using CRISPR/Cas9. Biochim Biophys Acta. 2016;1863:2333–2344. doi: 10.1016/j.bbamcr.2016.06.009. PubMed DOI

CHAN B, CLASQUIN M, SMOLEN GA, HISTEN G, POWE J, CHEN Y, LIN Z, LU C, LIU Y, CANG Y, YAN Z, XIA Y, THOMPSON R, SINGLETON C, DORSCH M, SILVERMAN L, SU SM, FREEZE HH, JIN S. A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2. Hum Mol Genet. 2016;25:2182–2193. doi: 10.1093/hmg/ddw085. PubMed DOI PMC

CHAVANAS S, BODEMER C, ROCHAT A, HAMEL-TEILLAC D, ALI M, IRVINE AD, BONAFE JL, WILKINSON J, TAIEB A, BARRANDON Y, HARPER JI, De PROST Y, HOVNANIAN A. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25:141–142. doi: 10.1038/75977. PubMed DOI

CHITAYAT D, HAJ-CHAHINE S, STALKER HJ, AZOUZ EM, COTE A, HALAL F. Hyperphalangism, facial anomalies, hallux valgus, and bronchomalacia: a new syndrome? Am J Med Genet. 1993;45:1–4. doi: 10.1002/ajmg.1320450103. PubMed DOI

CROSBY JR, SEIFERT RA, SORIANO P, BOWEN-POPE DF. Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages. Nat Genet. 1998;18:385–388. doi: 10.1038/ng0498-385. PubMed DOI

DeROSSI C, BODE L, EKLUND EA, ZHANG F, DAVIS JA, WESTPHAL V, WANG L, BOROWSKY AD, FREEZE HH. Ablation of mouse phosphomannose isomerase (Mpi) causes mannose 6-phosphate accumulation, toxicity, and embryonic lethality. J Biol Chem. 2006;281:5916–5927. doi: 10.1074/jbc.M511982200. PubMed DOI

DUPRE T, CUER M, BARROT S, BARNIER A, CORMIER-DAIRE V, MUNNICH A, DURAND G, SETA N. Congenital disorder of glycosylation Ia with deficient phosphomannomutase activity but normal plasma glycoprotein pattern. Clin Chem. 2001;47:132–134. doi: 10.1093/clinchem/47.1.132. PubMed DOI

DUPUY AJ, FRITZ S, LARGAESPADA DA. Transposition and gene disruption in the male germline of the mouse. Genesis. 2001;30:82–88. doi: 10.1002/gene.1037. PubMed DOI

FROGUEL P, VAXILLAIRE M, SUN F, VELHO G, ZOUALI H, BUTEL MO, LESAGE S, VIONNET N, CLÉMENT K, FOUGEROUSSE F, TANIZAWA Y, WEISSENBACH J, BECKMANN JS, LATHROP GM, PASSA P, PERMUTT MA, COHEN D. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Nature. 1992;356:162–164. doi: 10.1038/356162a0. PubMed DOI

FURIO L, PAMPALAKIS G, MICHAEL IP, NAGY A, SOTIROPOULOU G, HOVNANIAN A. KLK5 inactivation reverses cutaneous hallmarks of Netherton syndrome. PLoS Genet. 2015;11:e1005389. doi: 10.1371/journal.pgen.1005389. PubMed DOI PMC

GARRELS W, MATES L, HOLLER S, DALDA A, TAYLOR U, PETERSEN B, NIEMANN H, IZSVAK Z, IVICS Z, KUES WA. Germline transgenic pigs by Sleeping Beauty transposition in porcine zygotes and targeted integration in the pig genome. PLoS One. 2011;6:e23573. doi: 10.1371/journal.pone.0023573. PubMed DOI PMC

GOSSLER A, JOYNER AL, ROSSANT J, SKARNES WC. Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes. Science. 1989;244:463–465. doi: 10.1126/science.2497519. PubMed DOI

HARRIS SE, CHAND AL, WINSHIP IM, GERSAK K, NISHI Y, YANASE T, NAWATA H, SHELLING AN. INHA promoter polymorphisms are associated with premature ovarian failure. Mol Hum Reprod. 2005;11:779–784. doi: 10.1093/molehr/gah219. PubMed DOI

HOCH NC, HANZLIKOVA H, RULTEN SL, TETREAULT M, KOMULAINEN E, JU LM, HORNYAK P, ZENG ZH, GITTENS W, REY SA, STARAS K, MANCINI GMS, McKINNON PJ, WANG ZQ, WAGNER JD, YOON G, CALDECOTT KW, CONSORTIUM CRC. XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature. 2017;541:87–91. doi: 10.1038/nature20790. PubMed DOI PMC

JONES SN, ROE AE, DONEHOWER LA, BRADLEY A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of P53. Nature. 1995;378:206–208. doi: 10.1038/378206a0. PubMed DOI

KASPAREK P, ILENINOVA Z, HANECKOVA R, KANCHEV I, JENICKOVA I, SEDLACEK R. A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene. Biol Chem. 2016;397:1287–1292. doi: 10.1515/hsz-2016-0194. PubMed DOI

KASPAREK P, ILENINOVA Z, ZBODAKOVA O, KANCHEV I, BENADA O, CHALUPSKY K, BRATTSAND M, BECK IM, SEDLACEK R. KLK5 and KLK7 ablation fully rescues lethality of Netherton syndrome-like phenotype. PLoS Genet. 2017;13:e1006566. doi: 10.1371/journal.pgen.1006566. PubMed DOI PMC

KATTER K, GEURTS AM, HOFFMANN O, MATES L, LANDA V, HIRIPI L, MORENO C, LAZAR J, BASHIR S, ZIDEK V, POPOVA E, JERCHOW B, BECKER K, DEVARAJ A, WALTER I, GRZYBOWKSI M, CORBETT M, FILHO AR, HODGES MR, BADER M, IVICS Z, JACOB HJ, PRAVENEC M, BOSZE Z, RULICKE T, IZSVAK Z. Transposon-mediated transgenesis, transgenic rescue, and tissue-specific gene expression in rodents and rabbits. FASEB J. 2013;27:930–941. doi: 10.1096/fj.12-205526. PubMed DOI PMC

LINDAHL P, HELLSTROM M, KALEN M, KARLSSON L, PEKNY M, PEKNA M, SORIANO P, BETSHOLTZ C. Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli. Development. 1998;125:3313–3322. PubMed

LUNA RMD, WAGNER DS, LOZANO G. Rescue of early embryonic lethality in Mdm2-deficient mice by deletion of P53. Nature. 1995;378:203–206. doi: 10.1038/378203a0. PubMed DOI

MANSOUR SL, THOMAS KR, CAPECCHI MR. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988;336:348–352. doi: 10.1038/336348a0. PubMed DOI

MATZUK MM, FINEGOLD MJ, SU JG, HSUEH AJ, BRADLEY A. Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature. 1992;360:313–319. doi: 10.1038/360313a0. PubMed DOI

MOUNKES LC, KOZLOV S, HERNANDEZ L, SULLIVAN T, STEWART CL. A progeroid syndrome in mice is caused by defects in A-type lamins. Nature. 2003;423:298–301. doi: 10.1038/nature01631. PubMed DOI

NIEHUES R, HASILIK M, ALTON G, KORNER C, SCHIEBE-SUKUMAR M, KOCH HG, ZIMMER KP, WU RR, HARMS E, REITER K, Von FIGURA K, FREEZE HH, HARMS HK, MARQUARDT T. Carbohydrate-deficient glycoprotein syndrome type Ib - Phosphomannose isomerase deficiency and mannose therapy. J Clin Inv. 1998;101:1414–1420. doi: 10.1172/JCI2350. PubMed DOI PMC

OHMURAYA M, HIROTA M, ARAKI M, MIZUSHIMA N, MATSUI M, MIZUMOTO T, HARUNA K, KUME S, TAKEYA M, OGAWA M, ARAKI K, YAMAMURA K. Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal type 3-deficient mice. Gastroenterology. 2005;129:696–705. doi: 10.1053/j.gastro.2005.05.057. PubMed DOI

OKADA Y, UESHIN Y, ISOTANI A, SAITO-FUJITA T, NAKASHIMA H, KIMURA K, MIZOGUCHI A, OH-HORA M, MORI Y, OGATA M, OSHIMA RG, OKABE M, IKAWA M. Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer. Nat Biotechnol. 2007;25:233–237. doi: 10.1038/nbt1280. PubMed DOI

ONDRUSKOVA N, HONZIK T, VONDRACKOVA A, TESAROVA M, ZEMAN J, HANSIKOVA H. Glycogen storage disease-like phenotype with central nervous system involvement in a PGM1-CDG patient. Neuro Endocrinol Lett. 2014;35:137–141. PubMed

PIERSON TM, WANG Y, DEMAYO FJ, MATZUK MM, TSAI SY, OMALLEY BW. Regulable expression of inhibin A in wild-type and inhibin alpha null mice. Mol Endocrinol. 2000;14:1075–1085. doi: 10.1210/me.14.7.1075. PubMed DOI

POSTIC C, SHIOTA M, NISWENDER KD, JETTON TL, CHEN YJ, MOATES JM, SHELTON KD, LINDNER J, CHERRINGTON AD, MAGNUSON MA. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem. 1999;274:305–315. doi: 10.1074/jbc.274.1.305. PubMed DOI

ROSSANT J, CROSS JC. Placental development: lessons from mouse mutants. Nat Rev Genet. 2001;2:538–548. doi: 10.1038/35080570. PubMed DOI

SAKATA K, ARAKI K, NAKANO H, NISHINA T, KOMAZAWA-SAKON S, MURAI S, LEE GE, HASHIMOTO D, SUZUKI C, UCHIYAMA Y, NOTOHARA K, GUKOVSKAYA AS, GUKOVSKY I, YAMAMURA K, BABA H, OHMURAYA M. Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome. Sci Rep. 2016;6:37200. doi: 10.1038/srep37200. PubMed DOI PMC

SALES KU, MASEDUNSKAS A, BEY AL, RASMUSSEN AL, WEIGERT R, LIST K, SZABO R, OVERBEEK PA, BUGGE TH. Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat Genet. 2010;42:676–683. doi: 10.1038/ng.629. PubMed DOI PMC

SCHNEIDER A, THIEL C, RINDERMANN J, DEROSSI C, POPOVICI D, HOFFMANN GF, GRONE HJ, KORNER C. Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice. Nat Med. 2011;18:71–73. doi: 10.1038/nm.2548. PubMed DOI

SCHUBERT D, BODE C, KENEFECK R, HOU TZ, WING JB, KENNEDY A, BULASHEVSKA A, PETERSEN BS, SCHAFFER AA, GRUNING BA, UNGER S, FREDE N, BAUMANN U, WITTE T, SCHMIDT RE, DUECKERS G, NIEHUES T, SENEVIRATNE S, KANARIOU M, SPECKMANN C, ET AL. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014;20:1410–1416. doi: 10.1038/nm.3746. PubMed DOI PMC

SHACKLETON S, LLOYD DJ, JACKSON SNJ, EVANS R, NIERMEIJER MF, SINGH BM, SCHMIDT H, BRABANT G, KUMAR S, DURRINGTON PN, GREGORY S, O’RAHILLY S, TREMBATH RC. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000;24:153–156. doi: 10.1038/72807. PubMed DOI

SHARMA V, NAYAK J, DEROSSI C, CHARBONO A, ICHIKAWA M, NG BG, GRAJALES-ESQUIVEL E, SRIVASTAVA A, WANG L, HE P, SCOTT DA, RUSSELL J, CONTRERAS E, GUESS CM, KRAJEWSKI S, Del RIO-TSONIS K, FREEZE HH. Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice. FASEB J. 2014;28:1854–1869. doi: 10.1096/fj.13-245514. PubMed DOI PMC

SONG Y, SUI T, ZHANG Y, WANG Y, CHEN M, DENG J, CHAI Z, LAI L, LI Z. Genetic deletion of a short fragment of glucokinase in rabbit by CRISPR/Cas9 leading to hyperglycemia and other typical features seen in MODY-2. Cell Mol Life Sci. 2020;77:3265–3277. doi: 10.1007/s00018-019-03354-4. PubMed DOI PMC

SUI T, LIU D, LIU T, DENG J, CHEN M, XU Y, SONG Y, OUYANG H, LAI L, LI Z. LMNA-mutated rabbits: A model of premature aging syndrome with muscular dystrophy and dilated cardiomyopathy. Aging Dis. 2019;10:102–115. doi: 10.14336/AD.2018.0209. PubMed DOI PMC

SULLIVAN T, ESCALANTE-ALCALDE D, BHATT H, ANVER M, BHAT N, NAGASHIMA K, STEWART CL, BURKE B. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol. 1999;147:913–920. doi: 10.1083/jcb.147.5.913. PubMed DOI PMC

TEBBS RS, FLANNERY ML, MENESES JJ, HARTMANN A, TUCKER JD, THOMPSON LH, CLEAVER JE, PEDERSEN RA. Requirement for the Xrcc1 DNA base excision repair gene during early mouse development. Dev Biol. 1999;208:513–529. doi: 10.1006/dbio.1999.9232. PubMed DOI

TEBBS RS, THOMPSON LH, CLEAVER JE. Rescue of Xrcc1 knockout mouse embryo lethality by transgene-complementation. DNA Repair. 2003;2:1405–1417. doi: 10.1016/j.dnarep.2003.08.007. PubMed DOI

TERAUCHI Y, SAKURA H, YASUDA K, IWAMOTO K, TAKAHASHI N, ITO K, KASAI H, SUZUKI H, UEDA O, KAMADA N, JISHAGE K, KOMEDA K, NODA M, KANAZAWA Y, TANIGUCHI S, MIWA I, AKANUMA Y, KODAMA T, YAZAKI Y, KADOWAKI T. Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose. J Biol Chem. 1995;270:30253–30256. doi: 10.1074/jbc.270.51.30253. PubMed DOI

THIEL C, LUBKE T, MATTHIJS G, Von FIGURA K, KORNER C. Targeted disruption of the mouse phosphomannomutase 2 gene causes early embryonic lethality. Mol Cell Biol. 2006;26:5615–5620. doi: 10.1128/MCB.02391-05. PubMed DOI PMC

TWIGG SRF, VORGIA E, McGOWAN SJ, PERAKI I, FENWICK AL, SHARMA VP, ALLEGRA M, ZARAGKOULIAS A, AKHA ES, KNIGHT SJL, LORD H, LESTER T, IZATT L, LAMPE AK, MOHAMMED SN, STEWART FJ, VERLOES A, WILSON LC, HEALY C, SHARPE PT, HAMMOND P, HUGHES J, TAYLOR S, JOHNSON D, WALL SA, MAVROTHALASSITIS G, WILKIE AOM. Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis. Nat Genet. 2013;45:308–313. doi: 10.1038/ng.2539. PubMed DOI PMC

WANG H, YANG H, SHIVALILA CS, DAWLATY MM, CHENG AW, ZHANG F, JAENISCH R. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153:910–918. doi: 10.1016/j.cell.2013.04.025. PubMed DOI PMC

WANG L, LI MY, QU C, MIAO WY, YIN Q, LIAO J, CAO HT, HUANG M, WANG K, ZUO E, PENG G, ZHANG SX, CHEN G, LI Q, TANG K, YU Q, LI Z, WONG CC, XU G, JING N, YU X, LI J. CRISPR-Cas9-mediated genome editing in one blastomere of two-cell embryos reveals a novel Tet3 function in regulating neocortical development. Cell Res. 2017;27:815–829. doi: 10.1038/cr.2017.58. PubMed DOI PMC

WANG YL, O’MALLEY BW, JR, TSAI SY, O’MALLEY BW. A regulatory system for use in gene-transfer. Proc Natl Acad Sci U S A. 1994;91:8180–8184. doi: 10.1073/pnas.91.17.8180. PubMed DOI PMC

WATERHOUSE P, PENNINGER JM, TIMMS E, WAKEHAM A, SHAHINIAN A, LEE KP, THOMPSON CB, GRIESSER H, MAK TW. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270:985–988. doi: 10.1126/science.270.5238.985. PubMed DOI

WHITEHOUSE CJ, TAYLOR RM, THISTLETHWAITE A, ZHANG H, KARIMI-BUSHERI F, LASKO DD, WEINFELD M, CALDECOTT KW. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell. 2001;104:107–117. doi: 10.1016/S0092-8674(01)00195-7. PubMed DOI

WITT H, LUCK W, HENNIES HC, CLASSEN M, KAGE A, LASS U, LANDT O, BECKER M. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet. 2000;25:213–216. doi: 10.1038/76088. PubMed DOI

WU Y, ZHANG J, PENG B, TIAN D, ZHANG D, LI Y, FENG X, LIU J, LI J, ZHANG T, LIU X, LU J, CHEN B, WANG S. Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos. Nat Commun. 2019;10:2883. doi: 10.1038/s41467-019-10748-2. PubMed DOI PMC

XIAO ZX, CHEN JD, LEVINE AJ, MODJTAHEDI N, XING J, SELLERS WR, LIVINGSTON DM. Interaction between the retinoblastoma protein and the oncoprotein Mdm2. Nature. 1995;375:694–698. doi: 10.1038/375694a0. PubMed DOI

YAMAMOTO H, FLANNERY ML, KUPRIYANOV S, PEARCE J, McKERCHER SR, HENKEL GW, MAKI RA, WERB Z, OSHIMA RG. Defective trophoblast function in mice with a targeted mutation of Ets2. Genes Dev. 1998;12:1315–1326. doi: 10.1101/gad.12.9.1315. PubMed DOI PMC

YANG DS, XU J, ZHU TQ, FAN JL, LAI LX, ZHANG JF, CHEN YE. Effective gene targeting in rabbits using RNA-guided Cas9 nucleases. J Mol Cell Biol. 2014;6:97–99. doi: 10.1093/jmcb/mjt047. PubMed DOI PMC

YANG T, LIANG D, KOCH PJ, HOHL D, KHERADMAND F, OVERBEEK PA. Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5−/− mice. Genes Dev. 2004;18:2354–2358. doi: 10.1101/gad.1232104. PubMed DOI PMC

YOSHIMI K, KANEKO T, VOIGT B, MASHIMO T. Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR-Cas platform. Nat Commun. 2014;5:4240. doi: 10.1038/ncomms5240. PubMed DOI PMC

ZABOIKIN M, ZABOIKINA T, FRETER C, SRINIVASAKUMAR N. Non-homologous end joining and homology directed DNA repair frequency of double-stranded breaks introduced by genome editing reagents. PLoS One. 2017;12:e0169931. doi: 10.1371/journal.pone.0169931. PubMed DOI PMC

ZENG H, HORIE K, MADISEN L, PAVLOVA MN, GRAGEROVA G, ROHDE AD, SCHIMPF BA, LIANG Y, OJALA E, KRAMER F, ROTH P, SLOBODSKAYA O, DOLKA I, SOUTHON EA, TESSAROLLO L, BORNFELDT KE, GRAGEROV A, PAVLAKIS GN, GAITANARIS GA. An inducible and reversible mouse genetic rescue system. PLoS Genet. 2008;4:e1000069. doi: 10.1371/journal.pgen.1000069. PubMed DOI PMC

ZHANG YL, TAN XH, XIAO MF, LI H, MAO YQ, YANG X, TAN HR. Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs. Acta Pharmacol Sin. 2004;25:1659–1665. PubMed

ZINGKOU E, PAMPALAKIS G, SOTIROPOULOU G. Cathelicidin represents a new target for manipulation of skin inflammation in Netherton syndrome. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165831. doi: 10.1016/j.bbadis.2020.165831. PubMed DOI