Mice that are homozygous for this targeted mutation of Vip (vasoactive intestinal polypeptide) exhibit impaired circadian rhythm generation, muscle weakness, increased induced airway hyperresponsiveness/inflammation, gastrointestinal tract abnormalities. Male homozygotes exhibit moderate right ventricular hypertension and hypertrophy, reduced serum testosterone and follicle-stimulating hormone levels. All offspring of heterozygous females exhibit developmental delays such as reduced body weight and impaired social behavior. This mutant mouse strain may be useful in studies of embryonic and neonatal development, circadian rhythm, airway hyperresponsiveness and inflammation(asthma), gastrointestinal innervation and motility and idiopathic pulmonary arterial hypertension.
James Waschek, UCLA
Mice that are heterozygous for the targeted mutation are viable and fertile. No gene product (protein) is detected by immunohistochemical analysis of homozygotes. Homozygous females are subfertile, 15-20% of homozygous females can have litters. Homozygotes exhibit impaired circadian rhythm generation, muscle weakness, increased motor activity and increased induced airway hyperresponsiveness and inflammation. In constant darkness, homozygotes initially display shortened circadian period. Some homozygotes develop arrhythmic circadian periods after extended darkness. Heterozygotes also display abnormal circadian rhythm. Homozygotes have both gross and microscopic anatomical abnormalities of the gastrointestinal tract. 10-15% of homozygotes die of stenosis of the gut before one year of age. Male homozygotes exhibit moderate right ventricular (RV) hypertension, RV hypertrophy, thickened and remodeled pulmonary arteries, perivascular inflammation of smaller pulmonary vessels and airways, reduced serum testosterone levels, and reduced serum follicle-stimulating hormone (FSH) levels. Although male homozygotes had early testicular degeneration, age-dependent degeneration is slowed. All offspring of heterozygous females exhibit developmental delays such as reduced body weight and impaired social behavior. This mutant mouse strain may be useful in studies of embryonic and neonatal development, circadian rhythm, airway hyperresponsiveness and inflammation (asthma), gastrointestinal innervation and motility and idiopathic pulmonary arterial hypertension.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 4. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice, and then backcrossed to C57BL/6J (see SNP notes) for 12 generations.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Christopher S Colwell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||VIP KO; VIP/PHI-; VIP-|
|Gene Symbol and Name||Vip, vasoactive intestinal polypeptide|
|Strain of Origin||129/Sv|
|Molecular Note||A neomycin resistance gene was inserted in reverse orientation into exon 4. PCR confirmed recombination in mutant mice. Immunohistochemistry confirmed the loss of protein in homozygotes.|
|Mutations Made By|| |
James Waschek, UCLA
When maintaining a live colony, these mice are bred as heterozygous females and homozygous males. Homozygous females are subfertile; 15-20% of homozygous females can have litters .
When using the B6.129S4-Viptm1Clw/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009640 in your Materials and Methods section.