B6;129P2-Olfr78^tm1Mom/MomJ

Stock number: 006722
Product name: GFP→MOR18-2-IRES-taulacZ
Strain synonyms: GFP/MOR18-2-IRES-taulacZ, clone D18-268,
Research areas: Cardiovascular Research, Internal/Organ Research, Metabolism Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

This null allele with a taulacZ reporter is valuable for research into not only olfaction, but regulation of breathing by the carotid body, regulation of blood pressure through the renal system, and host interaction with the gut microbiota through responses to short chain fatty acids.

Detailed description

With the coding sequence of class I olfactory receptor Olfr78 excised and replaced with GFP and taulacZ, this strain allows assessment of the role of a specific olfactory receptor in olfactory sensory neuron development. Mice carrying this allele display a normal pattern of labeled axons projecting diffusely to a large subset of glomeruli in the dorsal-medial and anterior-medial olfactory bulb, but also an abnormal finding of labeled axons innervating glomeruli at the caudal margins of the olfactory bulb. Co-staining for five dorsal class II olfactory receptors shows 2.9% co-expressing class II olfactory receptor genes and the disrupted Olfr78^tm1Mom allele, while co-staining for five dorsal class I olfactory receptors shows no co-expression with the disrupted Olfr78^tm1Mom allele (Bozza et al., 2009). In addition to expression in olfactory sensory neurons, OLFR78 is also expressed in the juxtaglomerular afferent arteriole and the major branches of the renal artery and has been found to be a receptor for the short chain fatty acids acetate and propionate. Relative to wild-type littermates, homozygotes have a lower basal mean arterial blood pressure, 81.4 instead of 94.5 mmHg, and fail to increase renin levels in response to dietary plant polysaccharides. The normal hypotensive response to propionate is more severe in homozygotes than wild-type littermates. Gut microbiota contribute to blood pressure regulation, in part through metabolic byproducts, and although homozygotes have a comparable gut microbiota to wild-type siblings, treatment of homozygotes with antibiotics resulted in a significant increase in mean arterial blood pressure, but no change in heart rate, compared with antibiotic-treated wild-type siblings (Pluznick et al., 2013). Olfr78 was found to be expressed in the smooth muscle cells of small blood vessels in the heart, diaphragm, skeletal muscle and skin, and in axons of autonomic neurons in the heart and enteric plexus of the esophagus and stomach (Pluznick et al., 2013). Olfr78 is also expressed in the glomus cells of the carotid body and has been reported to be essential for hypoxia detection and response (Chang et al., 2015). Homozygotes lacking OLFR78 fail to increase respiration in response to hypoxia, and carotid sinus nerves from homozygotes respond to changes in pH but fail to respond to acetate, proprionate, or increased lactate.

Development

The coding sequence of Olfr78 was replaced with GFP, an IRES-taulacZ and the self-excising ACNf neomycin resistance cassette and the construct was used for homologous recombination in 129P2/OlaHsd derived E14 ES cells. A founder from clone D18-268 was bred to C57BL/6J females

Allele

Symbol: Or51e2^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:3722382
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Or51e2
Marker name: olfactory receptor family 51 subfamily E member 2
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Molecular note: The coding sequence was replaced with GFP, an IRES-taulacZ and self-excising neomycin resistance cassette were placed downstream, and clone D18-268 was used to generate this allele.