B6.129S6-Cftr^tm1Kth/J

Stock number: 002515
Product name: ΔF
Research areas: Immunology, Inflammation and Autoimmunity Research, Metabolism Research, Mouse/Human Gene Homologs

Description

These Cftr knock-out mice exhibit neonatal lethality with abnormal bowel development. They may be useful in applications related to the study of cystic fibrosis.

Detailed description

The Cftr^tm1Kth targeted mutation corresponds to the delta 508 mutation in humans. Homozygous mutant mice show an increased mortality within the first month after birth, with ~60% mortality by post-weaning. Those that survive are fertile, but females are poor breeders. Mutant mice are also reduced in size compared to normal wildtype mice. Those that do not survive to adulthood show bowel obstructions, bowel strictures and peritonitis. Lungs, pancreas, gall bladder, male reproductive tract, lacrimal gland, and submandibular glands from homozygous mice appear normal regardless of the survival of the animal. Homozygous mice also show a tissue-specific loss of CFTR transcripts in the intestine.

Development

The Cftr^tm1Kth targeted mutation was made in the laboratory of Dr. Kirk R. Thomas at the University of Utah. The mutated allele contains a 3-bp (CTT) deletion between bases 1656 and 1660 resulting in the loss of a phenylalanine residue in exon 10 at a position which corresponds to human position 508. The 129S6/SvEv-derived CC1.2 ES cell line was used.

Allele

Symbol: Cftr^tm1Kth
Name: targeted mutation 1, Kirk R Thomas
MGI accession ID: MGI:1857151
Generation method: Targeted
Attributes: Hypomorph
Marker symbol: Cftr
Marker name: cystic fibrosis transmembrane conductance regulator
Chromosome: 6
Strain of origin: 129S7/SvEvBrd
Molecular note: The allele contains a 3 bp deletion in exon 11 resulting in the loss of phenylalanine codon 508 (p.F508del). This deletion mimics the deltaF508 mutation found in human cystic fibrosis patients. A neomycin selection cassette was also inserted in intron 11 in reverse transcriptional orientation to the gene. In salivary glands transcription levels from the allele are comparable to wild-type, but no protein was detected. Protein was detected in testes but it was mislocalized. Transcription levels in intestine were greatly reduced.
General note: This (J:29074) and other (J:27734, J:28979) targeted mutations reproduce the common human mutation, eliminating the same phenylalanine from the protein sequence. In at least one of these models, the mutant is temperature sensitive, and can be expressed on the apical membrane when cultured at low temperatures, which is also true of the human mutant lacking the same phenylalanine residue (J:35364).