STOCK Tg(Fabp2-CFTR*)1Wsh/J

Stock number: 017957
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

This transgenic strain carries a truncated form of human CFTR (cystic fibrosis transmembrane conductance regulator) under the control of a rat Fabp2 (fatty acid binding protein 2, intestinal) promoter. When crossed with a Cftr knockout mouse the lethal intestinal blockage phenotype associated with cystic fibrosis is rescued and corrected.

Detailed description

Current therapeutic technologies that apply adeno-associated virus (AAV) gene transfer are limited by viral packaging capacity. Some full-length genes, like Cftr (cystic fibrosis transmembrane conductance regulator) have not been practical candidates for these therapies.

This transgenic strain, carrying a truncated form of human CFTR under the control of a rat Fabp2 (fatty acid binding protein 2, intestinal) promoter, was used to study the potential of shortened genetic segments in the treatment of cystic fibrosis. The N-terminal portion of the regulatory (R) domain was deleted (residues 708-759), but regulated anion channel activity is retained in vitro. When crossed with a Cftr knockout mouse (see Stock No. 002196), the intestinal blockage phenotype associated with cystic fibrosis is rescued and corrected. The gross morphology of both small and large intestines is restored and the excessive mucus observed in the crypts of Cftr knockout mice is reduced.

Development

Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein (Fabp2) promoter drive expression of a human CFTR cDNA from which sequences encoding N-terminal residues 708-759 (nucleotides 2254-2409) have been deleted (Ref Seq NM_000492). This transgenic strain was created with C57BL/6 x SJL/J F1 embryos, but maintained on a mixed genetic background incorporating C57BL/6, 129, BALB/c, FVB, and SJL genetic contributions by the donating laboratory.

Allele

Symbol: Tg(Fabp2-CFTR*)1Wsh
Name: transgene insertion 1, Michael J Welsh
MGI accession ID: MGI:5308021
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: CFTRdeltaR
Marker symbol: Tg(Fabp2-CFTR*)1Wsh
Marker name: transgene insertion 1, Michael J Welsh
Chromosome: UN
Strain of origin: (C57BL/6 x SJL/J)F1
Expressed genes: CFTR,cystic fibrosis transmembrane conductance regulator,human
Molecular note: Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein (Fabp2) promoter drive expression of a human CFTR cDNA from which sequences encoding N-terminal residues 708-759 have been deleted. Line 1 was generated.