129S-Npy^tm1Rpa/J

Stock number: 004545
Product name: NPY KO
Research areas: Diabetes and Obesity Research, Neurobiology Research, Research Tools

Description

Homozygous mutants in this lacZ reporter strain exhibit spontaneous and GABA induced seizures. These mice may be useful in studies related to the role of neuropeptide Y in obesity.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of brain or adrenal gland tissue. Beta-galactosidase activity assays and in situ hybridization demonstrate similar expression patterns for the lacZ gene and the endogenous wildtype gene. Spontaneous seizures are exhibited by some mice at age 6 to 8 weeks. Homozygous mice are susceptible to seizures induced by GABA antagonist treatment. Mutant mice have an increased sensitivity to leptin treatment which results in a greater initial reduction of food intake and weight loss when compared to wildtype mice. This mutant mouse strain may be useful in studies related to the role of neuropeptide Y in obesity.

Development

A targeting vector containing neomycin resistance, thymidine kinase and lacZ reporter genes was used to disrupt exon 2 of the targeted gene. The construct was electroporated into 129S7/SvEvBrd-Hprt⁺ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Allele

Symbol: Npy^tm1Rpa
Name: targeted mutation 1, Richard D Palmiter
MGI accession ID: MGI:2182113
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Npy
Marker name: neuropeptide Y
Chromosome: 6
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ replaces/mimics endogenous gene expression
Molecular note: Exon 2, which encodes the signal peptide and 35 amino acids, was replaced by a lacZ-neo fusion gene. The expression pattern of the beta-galactosidase was shown to resemble that of the endogenous gene via comparisons of X-gal staining and previous in situ hybridization studies. RT-PCR analysis of brain tissue showed an absence of transcript in homozygous mutant mice.