B6.129X1-Wasf1^tm1Jsco/J

Stock number: 007445
Product name: WAVE-1 KO
Research areas: Developmental Biology Research, Neurobiology Research

Description

Homozygous mutants exhibit morphological and functional defects of the central nervous with symptoms are similar to those of patients with 3p-syndrome mental retardation.

Detailed description

Viability of Wasf1 KO homozygotes is reduced; approximately 20% die within the first week of life. These animals are small in size, have impaired neurite outgrowth, impaired spinogenesis, elevated long-term potentiation (LTP), decreased long-term depression (LTD), and behavioral abnormalities including reduced sensorimotor function, reduced anxiety and impaired learning and memory (both spatial and non-spatial). Some symptoms are similar to those of patients with 3p-syndrome mental retardation. Protein derived from the targeted locus is absent from brain samples as assessed by immunoblot in mice homozygous for this allele.

Of note, other Wasf1 KO mutations have been used to study the brain's response during addiction to cocaine. These mice exhibit a significant decrease in the preference for cocaine.

Development

A targeting vector was designed to replace the 3' end of exon 4 and a segment of intron 5 of the WAS protein family, member 1 (Wasf1) gene with a uracil and neomycin selection cassette. An in-frame stop codon at amino acid 175 and a deletion of 95 bp including the splice donor site of exon 4 were created. The construct was electroporated into 129X1/SvJ-derived JSI-1 embryonic stem (ES) cells. Germline chimeric mice were backcrossed to C57BL/6J for a minimum of 10 generations by the donating laboratory.

Allele

Symbol: Wasf1^tm1Jsco
Name: targeted mutation 1, John D Scott
MGI accession ID: MGI:2451310
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: wave^-
Marker symbol: Wasf1
Marker name: WAS protein family, member 1
Chromosome: 10
Strain of origin: 129X1/SvJ
Molecular note: Exon 4 was replaced with a cassette containing both uracil- and neomycin-resistance genes. The insertion deleted 95 bp, including the splice donor site of exon 4, and introduced a nonsense mutation at codon 175. Normal protein was undetected by Western blot analysis of homozygous mutant brain tissue.
General note: ES cell line = JSI-1.