129S-Wwtr1^tm1Benj/J

Stock number: 011120
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research

Description

Mice that are homozygous for this targeted mutation develop renal cysts, swollen alveoli and alveolar wall degradation. This mutant mouse strain may be useful in studies of polycystic kidney disease and emphysema.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, small in size and less active than wildtype controls. Only 10-25% of the expected homozygotes are born. The Donating Investigator reports that breeding homozygous females successfully is uncommon and homozygotes usually succumb before breeding age. No gene product (protein) is detected by Western blot analysis. Homozygotes develop severe polycystic renal disease, with an onset as early as a few weeks of age, and emphysema, with swollen alveoli and breakdown of alveolar walls. Kidney size increases with age. Intestinal and pulmonary inflammation is observed in some homozygotes. Levels of protein polycystin 2 (PC2) is increased in kidney epithelial cells of homozygotes. Histological analysis reveals adipocytes are smaller than wildtype control.

Development

A targeting vector containing the lacZ gene, neomycin resistance cassette and diphtheria toxin A chain selection cassette was used to disrupt exon 2, which encodes the first 144 amino acids. The construct was electroporated into 129S6/SvEv derived PluriStem 129/S6 Murine embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTAC mice and maintained on the same background by the Donating Investigator. Upon arrival at The Jackson Laboratory, the mice were crossed once to 129S1/SvImJ inbred mice (Stock No. 002448) to establish the colony.

Allele

Symbol: Wwtr1^tm1Benj
Name: targeted mutation 1, Thomas Benjamin
MGI accession ID: MGI:3759999
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Wwtr1
Marker name: WW domain containing transcription regulator 1
Chromosome: 3
Strain of origin: 129S6/SvEvTac
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: Exon 2 was replaced with a SA-Betagal PGK-neo cassette such that the remaining open reading frame would be out of frame. Exon 2 encodes a 144 amino acid stretch containing the 14-3-3 binding domain and the WW domain. A western blot of protein extracts from mouse embryonic fibroblasts with a C-terminal antibody confirmed the absence of protein expression.