STOCK Nrp1^tm1.1Chgu/J

Stock number: 037627
Product name: Nrp1^VEGF-
Research areas: Cardiovascular Research, Sensorineural Research

Description

Nrp1^VEGF- carry a D320K mutation in exon 6 of the mouse neuropilin 1 (Nrp1) gene that selectively disrupts binding to VEGF (vascular endothelial growth factor), a key regulator of angiogenesis.

Detailed description

Nrp1 (neuropilin 1) is essential for vascular morphogenesis and encodes a receptor that binds VEGF (vascular endothelial growth factor), a key regulator of angiogenesis.

Nrp1^VEGF- mice carry a D320K mutation in exon 6 of the mouse Nrp1 gene that selectively disrupts binding to VEGF without disrupting AP-SEMA3A binding. Western blot analysis indicates protein expression levels are similar to wildtype controls at E14.5 in the lung and in the adult heart, brain, lung and kidney.

The mice are born at expected Mendelian ratios, display normal body weight, do not demonstrate any overt phenotype, and survive to adulthood with normal vasculature. They fail to develop the cardiac defects that have been observed in Nrp1 knock-out mice. A delay in vascular extension and a reduction in the number of arteries in the postnatal retina has been observed, however. Homozygotes also have delayed blood flow recovery following femoral artery ligation. The strain can be used to interrogate physiological phenomena's dependence of NRP1-VEGF interactions in vivo.

Development

A D320K (GAC->AAG) mutation was introduced into exon 6 (encoding the b1 extracellular domain) and an FRT-flanked neo cassette was inserted in intron 6 of the mouse Npr1 gene via homologous recombination in an unknown embryonic stem (ES) cell line. FlpE-mediated recombination removed the neo cassette. Resultant mice were backcrossed to C57BL/6NCrl for fewer than 5 generations by the donating laboratory.

Upon arrival at The Jackson Laboratory, sperm was cryopreserved. Cryorecovery/live colony development will involve C57BL/6NJ (Stock No. 005304).

Allele

Symbol: Nrp1^tm1.1Chgu
Name: targeted mutation 1.1, Chenghua Gu
MGI accession ID: MGI:5705771
Generation method: Targeted
Synonyms: Nrp1^VEGF-
Marker symbol: Nrp1
Marker name: neuropilin 1
Marker synonyms: BDCA4; CD304; Neuropilin-1; NP1; NP-1; Npn1; NPN-1; NRP; VEGF165R
Chromosome: 8
Strain of origin: Not Specified
Molecular note: A D320K mutation was introduced into exon 6 and an FRT flanked neo cassette was inserted in intron 6 via homologous recombination. Flp mediated recombination removed the neo cassette. The mutation in exon 6 disrupts binding to VEGF without disrupting AP-SEMA3A binding. Western blot analysis indicates protein expression level is similar to wild-type controls at E14.5 in the lung and in the adult heart, brain, lung and kidney.