Stimulation of beta adrenergic receptor function in homozygous null mice for the Adrb1 and Adrb2 genes by agonists or exercise reveals significant impairments in chronotropic range, vascular reactivity and metabolic rate. When exercised, heart rates in null mice are lower than that of wild type mice.
Dr. Brian Kobilka, Stanford University
Genetic Background | Generation |
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F7+3pF25
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Adrb1 | adrenergic receptor, beta 1 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Adrb2 | adrenergic receptor, beta 2 |
Mice that are homozygous null for the Adrb1 and Adrb2 genes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Stimulation of beta adrenergic receptor function in these mice by agonists or exercise reveals significant impairments in chronotropic range, vascular reactivity and metabolic rate. A severely attenuated chronotropic and hypotensive response is observed after administration of the non-selective beta adrenergic receptor agonist isoproterenol. An abnormal response to epinephrine is also seen, with bradycardia and a monophasic hypertensive blood pressure change being observed rather than the tachycardia and biphasic hypertensive/ hypotensive response seen in wildtype mice. When exercised, heart rates in null mice are lower than that of wild type mice. No difference is noted in the resting heart rate.
Double knockout mice were created by mating Adrb1 homozygous knockout mice with Adrb2 homozygous knockout mice to generate compound heterozygotes, the offspring of which were then mated to obtain compound homozygotes. Adrb1 null mice were created using a targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter to disrupt most of the Adrb1coding region (all but a 3' 153 bp). The construct was transfected into 129- derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were mated to C57BL/6J X DBA/2 F1 hybrids. Adrb2 null mice were created in a similar fashion using a targeting vector again containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter to disrupt Adrb2 such that the end of the fourth transmembrane segment is absent, rendering the receptor nonfunctional. The construct was transfected into 129- derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into CD-1 blastocysts. The resulting chimeric male animals were mated to FVB/N females.
Allele Name | targeted mutation 1, Brian K Kobilka |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Adrb1tm1Gsb; beta1-AR-; Beta1-KO |
Gene Symbol and Name | Adrb1, adrenergic receptor, beta 1 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 19 |
Molecular Note | A 1364 bp genomic fragment containing the initiation codon was replaced with a neomycin selection cassette. No protein product was detected on Western blots of heart tissue from homozygous mutant mice. |
Mutations Made By | Dr. Brian Kobilka, Stanford University |
Allele Name | targeted mutation 1, Brian K Kobilka |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Adrb2-; Beta2-AR; beta2AR-; Beta2-KO |
Gene Symbol and Name | Adrb2, adrenergic receptor, beta 2 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 18 |
Molecular Note | A neomycin selection cassette was inserted into the sequence encoding the fourth transmembrane segment. This mutation is predicted to eliminate expression of a functional receptor. Ligand binding experiments confirmed that no functional receptor was expressed in the lung of homozygous mice. |
Mutations Made By | Dr. Brian Kobilka, Stanford University |
These mice are maintained by mating double homozygote null mice. A number of strains have contributed to the background (C57BL/6J, DBA/2, 129, FVB/N, CD-1) which will be designated as STOCK.
When using the β1-AR-; β2-AR- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003810 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Homozygous for Adrb1<tm1Bkk>, Homozygous for Adrb2<tm1Bkk> |
Frozen Mouse Embryo | STOCK Adrb1tm1Bkk Adrb2tm1Bkk/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | STOCK Adrb1tm1Bkk Adrb2tm1Bkk/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | STOCK Adrb1tm1Bkk Adrb2tm1Bkk/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | STOCK Adrb1tm1Bkk Adrb2tm1Bkk/J Frozen Embryos | $3373.50 |
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