B6.129S7(129S6)-Del(17)4Mom/1MomJ

Stock number: 008097
Strain synonyms: B6.129-Del(17)4Mom/1MomJ strain A
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research

Description

This strain is valuable for studying vomeronasal sensory neuron signaling, chemodetection, and the role of MHC in pheromone detection.

Detailed description

Del(17)5Mom was made in the identical manner as the Del(17)4Mom deletion so is predicted to cause the same phenotype. This summary describes the data for the Del(17)5Mom deletion, most of which was assessed on a 129 genetic background. Homozygotes are devoid of the nine H2-Mv cluster genes, yet immunohistochemistry does not detect any compensatory increase in expression of MHC class I genes in the basal vomeronasal epithelium. The accessory olfactory bulb appears to develop normally, the tripartite layering of the vemeronasal epithelium is reasonably normal, but there is a minor decrease in the number of basal vomeronasal sensory neurons (VSN) in 10-week-old males. NanoString analysis at 3 weeks of age shows no difference in RNA expression in 37 different vomeronasal receptors, and at 8 weeks of age only a small reduction in expression of 3 out of 36 receptors: Vmn2r10, Vmn2r14, and Vmn2r70. Vmn2r81-expressing VMNs, which normally co-express H2-Mv, have a decreased sensitivity to two separate peptide ligands; Vmn2r26-expressing VMNs, which normally do not co-express H2-Mv, do not show this decreased sensitivity to stimulation. Although Vmn2r81-expressing VMNs show reduced ligand sensitivity, with higher ligand concentration they can still respond at the same maximum level. A diminished sensitivity was also found to stimulation from the high molecular weight fraction of C57BL/6 male urine and to exocrine gland secreted peptide 1. Both homozygous males and homozygous lactating females show decreased aggression toward a castrated intruder male that had been swabbed with high molecular weight fraction of male urine. This diminished aggression can be restored to approximately normal levels by increasing 4 fold the dose of male urine applied to the intruder. Although homozygous males show no change in latency to mount, and homozygous females show no change in duration of investigation of the male anogenital region, homozygous females do display diminished lordosis behavior.

Development

This 532,098 base pair deletion encompasses all nine genes in the H2-Mv cluster. Replacement vectors for each end of the H2-Mv gene cluster were electroporated consecutively into 129S7-derived, Hprt-deficient AB2.2 ES cells. One vector had an Hprt (5?)-loxP-neo cassette and the other had a puro-loxP-Hprt cassette. ES Cell clones with both targeted events were electroporated with the Cre-expression plasmid pOG231, and cultured in hypoxantine-aminopterin-thymidine to select for those clones in which Cre-recombination reconstituted a functional Hprt gene by deleting the large intervening sequence. Selected ES cells were injected into C57BL/6 blastocysts and male chimeras were bred to 129S6/SvEvTac producing stock #006730. This deletion was backcrossed for 5 generations onto C57BL/6J and homozygous sperm was cryopreserved from this congenic. Strains derived from this ES cell microinjection were referred to as strain A to distinguish them from strains derived from injecting a different ES cell clone, strains C (see stocks #006731 and #008098).

Allele

Symbol: Del(17)4Mom
Name: deletion, Chr 17, Peter Mombaerts 4
MGI accession ID: MGI:5558057
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Del(17)4Mom
Marker name: deletion, Chr 17, Peter Mombaerts 4
Chromosome: 17
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: Chromosome engineering produced this 532,098 base pair deletion from Chromosome 17 36,283,667bp to 26,815,764bp (GRCm38), and strains were generated from two separate chimeras with Line A assigned this deletion symbol and Line C assigned Del(17)5Mom.