OMIA:001794-9940 : Cystic fibrosis in Ovis aries (sheep)

In other species: domestic ferret , pig

Categories: Digestive / alimentary phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 219700 (trait) , 602421 (gene)

Links to MONDO diseases:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Species-specific description: Fan et al. (2018) "describe the generation of a sheep model for CF using CRISPR/Cas9 genome editing and somatic cell nuclear transfer (SCNT) techniques" and propose "the generation of specific human CF disease–associated mutations in sheep [to] ...advance personalized medicine for this common genetic disorder."

The same research team later developed models for the most common CSFR mutations found in human patients in the USA: "we describe the generation of CFTR^F508del/F508del and CFTR^G542X/G542X lambs using CRISPR/Cas9 and somatic cell nuclear transfer (SCNT)." (Perisse et al., 2021)

(Genetically-modifed organisms; GMO)

(Entry was edited by Hannah Edgell 24/08/2022)

Molecular basis: Fan et al. (2028) " generated cells with CFTR gene disruption [in exon 2 and exon 11] and used them for production of CFTR–/– and CFTR+/– lambs. The newborn CFTR–/– sheep developed severe disease consistent with CF pathology in humans."

Perisse et al. (2021) "introduced either F508del or G542X mutations into sheep fetal fibroblasts that were subsequently used as nuclear donors for SCNT. The newborn CF lambs develop pathology similar to CFTR -/- sheep and CF patients. Moreover, tracheal epithelial cells from the CFTRF508del / F508del lambs responded to a human CFTR (hCFTR) potentiator and correctors, and those from CFTRG542X / G542X lambs showed modest restoration of CFTR function following inhibition of nonsense-mediated decay (NMD) and aminoglycoside antibiotic treatments."

Breed: Romney (Sheep) (VBO_0001581).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CFTR cystic fibrosis transmembrane conductance regulator Ovis aries 4 NC_056057.1 (52438143..52249612) CFTR Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1479 Romney (Sheep) Cystic fibrosis CFTR nonsense (stop-gain) Genome-editing (CRISPR-Cas9) Oar_rambouillet_v1.0 4 g.57192317C>A c.1621G>T p.(G541*) NM_001009781.1; NP_001009781.1; published as p.(G542X), coordinates in this table are updated to recent reference sequence 2021 34632318
1478 Romney (Sheep) Cystic fibrosis CFTR deletion, small (<=20) Genome-editing (CRISPR-Cas9) Oar_rambouillet_v1.0 4 g.57218683_57218685del c.1518_1520del p.(F507del) NM_001009781.1; NP_001009781.1; published as p.(F508del), coordinates are updated in this table to recent reference sequence 2021 34632318

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001794-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Kerschner, J.L., Paranjapye, A., Schacht, M., Meckler, F., Huang, F., Bebek, G., Van Wettere, A.J., Regouski, M., Perisse, I.V., White, K.L., Polejaeva, I.A., Leir, S.H., Harris, A. :
Transcriptomic analysis of lung development in wildtype and CFTR-/- sheep suggests an early inflammatory signature in the CF distal lung. Funct Integr Genomics 23:135, 2023. Pubmed reference: 37085733 . DOI: 10.1007/s10142-023-01050-y.
2021 Périssé, I.V., Fan, Z., Van Wettere, A., Liu, Y., Leir, S.H., Keim, J., Regouski, M., Wilson, M.D., Cholewa, K.M., Mansbach, S.N., Kelley, T.J., Wang, Z., Harris, A., White, K.L., Polejaeva, I.A. :
Sheep models of F508del and G542X cystic fibrosis mutations show cellular responses to human therapeutics. FASEB Bioadv 3:841-854, 2021. Pubmed reference: 34632318 . DOI: 10.1096/fba.2021-00043.
2020 Menchaca, A., Dos Santos-Neto, P.C., Mulet, A.P., Crispo, M. :
CRISPR in livestock: From editing to printing. Theriogenology 150:247-254, 2020. Pubmed reference: 32088034 . DOI: 10.1016/j.theriogenology.2020.01.063.
2018 Fan, Z., Perisse, I.V., Cotton, C.U., Regouski, M., Meng, Q., Domb, C., Van Wettere, A.J., Wang, Z., Harris, A., White, K.L., Polejaeva, I.A. :
A sheep model of cystic fibrosis generated by CRISPR/Cas9 disruption of the CFTR gene. JCI Insight 3:, 2018. Pubmed reference: 30282831 . DOI: 10.1172/jci.insight.123529.

Edit History

  • Created by Imke Tammen2 on 19 Apr 2021
  • Changed by Imke Tammen2 on 24 Aug 2022