B6.129S7-Chrna3^tm1Bay/J

Stock number: 004164
Product name: α3-
Research areas: Neurobiology Research

Description

These Chrna3 knock-out mice exhibit increased mortality before and after weaning with bladder defects and unresponsive ocular pupils. They may be useful in applications related to the study of megacystis-microcolon-intestinal hypoperistalsis syndrome in humans.

Detailed description

On the C57BL/6J background, most mice homozygous for the targeted allele die during postnatal week 1-2 (On a 129 background, most survived to postnatal week 4-6). These older, surviving mice fail to open their eyes. Upon inspection, the eye is found to be smaller than that seen in wildtype mice with the pupil being widely dilated and unresponsive to light. The urinary bladders of these mice are severely distended with urine and in the case of older animals, urinary stones. Nicotine fails to elicit a contractile response in bladder tissue derived from homozygotes. Heterozygotes are phenotypically normal.

Development

A targeting vector containing hypoxanthine phosphoribosyltransferase (HPRT) and herpes simplex virus thymidine kinase genes was used to disrupt a region of the Chrna3 gene encoding exon 5. The construct was electroporated into 129S6/SvEvBrd-Hprt^b-m2-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were mated to C57BL/6 females.

Allele

Symbol: Chrna3^tm1Bay
Name: targeted mutation 1, Baylor College of Medicine
MGI accession ID: MGI:2155602
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Chrna3
Marker name: cholinergic receptor, nicotinic, alpha polypeptide 3
Chromosome: 9
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: A 1.8kb genomic fragment containing exon 3 was replaced by an HPRT minigene. These sequences encode three of the four transmembrane domains, the amphipathic helix domain and the four cysteines essential for ligand binding. No transcript produced from this allele was detectable by northern blotting.