In other species: domestic ferret , pig , rabbit

Categories: Digestive / alimentary phene

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

Links to MONDO diseases:

• MONDO:0009061: cystic fibrosis

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/F508de_l} 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."

Genetic engineering: Yes - variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

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: