Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) was detected. Homozygous mutant mice have elevated systolic, diastolic and mean blood pressure when compared to wildtype. Heterozygous mutant mice display systolic, diastolic and mean blood pressure that are slightly elevated above wildtype levels. Blood pressure in mutant mice remains elevated independent of salt content in diet. Infusion treatment of atrial natriuretic peptide in mutant mice does not result in the increased urine output or sodium excretion response seen in wildtype mice. Plasma volume expansion to release natriuretic/diuretic factors from the heart fails to induce increased urine output, sodium excretion and cyclic GMP excretion in the mutant. The same plasma volume expansion in wildtype mice results in a 12-fold increase in urine output, a 6-fold increase in sodium excretion and a 4-fold increase in c...
David L. Garbers, U.T. Southwestern Medical Center
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) was detected. Homozygous mutant mice have elevated systolic, diastolic and mean blood pressure when compared to wildtype. Heterozygous mutant mice display systolic, diastolic and mean blood pressure that are slightly elevated above wildtype levels. Blood pressure in mutant mice remains elevated independent of salt content in diet. Infusion treatment of atrial natriuretic peptide in mutant mice does not result in the increased urine output or sodium excretion response seen in wildtype mice. Plasma volume expansion to release natriuretic/diuretic factors from the heart fails to induce increased urine output, sodium excretion and cyclic GMP excretion in the mutant. The same plasma volume expansion in wildtype mice results in a 12-fold increase in urine output, a 6-fold increase in sodium excretion and a 4-fold increase in cyclic GMP excretion in the urine. Mutant mice excrete only 30% of the normal level of urinary cyclic GMP. The Donating Investigator reports this mutant strain also exhibits cardiac hypertrophy and cardiac fibrosis. The phenotype of this mutant strain, salt insensitive hypertension, resembles that of half of all human patients with essential hypertension. This mutant mouse strain represents a model that may be useful in studies related to essential hypertension.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 4 of the targeted gene. The construct was electroporated into 129S7/SvEvBrd-Hprt+ derived AB-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, David L Garbers|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||GC-A KO; GC-A-|
|Gene Symbol and Name||Npr1, natriuretic peptide receptor 1|
|Gene Synonym(s)||AI893888; ANPRA; ANPa; Anpra; GC-A; GUC2A; GUCY2A; Gca; NPR-A; NPRA; Npra; Pndr; expressed sequence AI893888; guanylyl cyclase-A|
|Strain of Origin||129S7/SvEvBrd-Hprt<+>|
|Molecular Note||Insertion of a neomycin resistance cassette into exon 4, which encodes part of the extra-cellular putative ligand-binding domain, disrupted the gene. Stable, wild-type size transcript was not detected in liver or kidney from homozygous mutant mice.|
|Mutations Made By|| |
David Garbers, U.T. Southwestern Medical Center
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