Strain Name:
STOCK Htr3atm1Ckn/Mmucd
Stock Number:
009966-UCD
Citation ID:
RRID:MMRRC_009966-UCD
Other Names:
5HT3 VS Cre Deleted, B6;129S1-Htr3atm1Ckn/Mmcd

Strain Information

Htr3atm1Ckn
Name: 5-hydroxytryptamine (serotonin) receptor 3A; targeted mutation 1, Debra A Cockayne
Synonyms: 5HT3Avs
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 7
Alteration at locus: Knock-In
Htr3a
Name: 5-hydroxytryptamine (serotonin) receptor 3A
Synonyms: 5-HT3 receptor
Type: Gene
Species: Mouse
Chromosome: 9
Alteration at locus: Knock-In
NCBI: 15561
VEGA: 9
HGNC: HGNC:5297
Homologene: 671
Genetic Alterations
Val13' within the putative pore-forming domain, M2, is mutated, predicting a substitution to (commonly referred to as V13'S), thus rendering the 5-HT3A homomeric receptor ~70 fold more sensitive to serotonin. In addition, a small molecular lesion, a 34-bp loxP sequence, is present in intron 5.

HGVS nomenclature
  • Genbank RefSeq - mRNA: NM_013561.2
  • Genbank RefSeq, protein: NP_038589.2
  • Variant, nucleic acid level: c.871_873delinsTCA
  • Variant, amino acid level, predicted: p.Val291Ser
    Check this variant: LUMC Mutalyzer
Note: It is unclear if this strain still carries the Cre allele from DBA/2-Tg(CAG-lacZ)36And/J (JAX Strain #002981).
Genotype Determination
ES Cell Line
CJ7 derived from 129S1/Sv-Oca2+ Tyr+ Kitl+
Phenotype
Mice homozygous for the mutant allele (5-HT3Avs/vs) had decreased levels of Htr3a mRNA. Measurements on sympathetic ganglion cells in these mice showed that whole-cell serotonin responses were reduced and that the remaining 5-HT3 receptors were hypersensitive. Male 5-HT3Avs/vs mice died at 2-3 months of age, and heterozygous (5-HT3Avs/+) males and homozygous mutant females died at 4-6 months of age from obstructive uropathy. Both male and female 5-HT3A mutant mice had urinary bladder mucosa and smooth muscle hyperplasia and hypertrophy, whereas male mutant mice had additional prostatic smooth muscle and urethral hyperplasia. 5-HT3A mutant mice had marked voiding dysfunction characterized by a loss of micturition contractions with overflow incontinence. Detrusor strips from 5-HT3Avs/vs mice failed to contract to neurogenic stimulation, despite overall normal responses to a cholinergic agonist, suggestive of altered neuronal signaling in mutant mouse bladders. Consistent with this hypothesis, decreased nerve fiber immunoreactivity was observed in the urinary bladders of 5-HT3Avs/vs compared with 5-HT3A wild-type (5-HT3A+/+) mice.

Heterozygote: milder uropathy
Mammalian Phenotype Terms
Allelic Composition: Htr3atm1Ckn/Htr3atm1Ckn (Genetic Background: involves: 129S1/Sv * C57BL/6J * DBA/2 )

Allelic Composition: Htr3atm1Ckn/Htr3a+ (Genetic Background: involves: 129S1/Sv * C57BL/6J * DBA/2 )

MeSH Terms
  • Animals
  • Animals, Newborn
  • Female
  • Humans
  • In Vitro Techniques
  • Isometric Contraction
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Muscle, Smooth/physiopathology
  • Nerve Fibers/pathology
  • Oocytes/physiology
  • Patch-Clamp Techniques
  • Point Mutation
  • Receptors, Serotonin, 5-HT3/biosynthesis
  • Receptors, Serotonin, 5-HT3/genetics
  • Urethra/physiopathology
  • Urinary Bladder/innervation
  • Urinary Bladder/pathology
  • Urinary Bladder/physiopathology
  • Urinary Bladder Neck Obstruction/mortality
  • Urinary Bladder Neck Obstruction/pathology
  • Urinary Bladder Neck Obstruction/physiopathology
  • Urodynamics
  • Xenopus
Strain Development
See PMID:15201326. The deletion of the loxP sites was accomplished with DBA/2-Tg(CAG-lacZ)36And/J (JAX Strain #002981); the allele might still be present. The strain contains genetic background components from C57BL/6J, 129S1/SvImJ, and DBA/2, requiring its designation as STOCK.
Suggested Control Mice
Wild-type littermates
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.
  • Models for Human Disease
  • Neurobiology
Donor
Debra A. Cockayne, Ph.D., Boston Scientific.
Henry Lester, Ph.D., California Institute of Technology.
Primary Reference

Bhattacharya A, Dang H, Zhu QM, Schnegelsberg B, Rozengurt N, Cain G, Prantil R, Vorp DA, Guy N, Julius D, Ford AP, Lester HA, Cockayne DA. Uropathic observations in mice expressing a constitutively active point mutation in the 5-HT3A receptor subunit. J Neurosci. 2004 Jun 16;24(24):5537-48. (Medline PMID: 15201326)

Zinyk DL, Mercer EH, Harris E, Anderson DJ, Joyner AL. Fate mapping of the mouse midbrain-hindbrain constriction using a site-specific recombination system. Curr Biol. 1998 May 21;8(11):665-8. (Medline PMID: 9635195)

Colony and Husbandry Information

Homozygous mice are not fertile and die at ~ 3-6 months of age. Heterozygous mice are fertile and live from 8-19 months. Heterozygous mice develop mild uropathy.

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.
Coat Color
Black and Brown
Eye
Black
MMRRC Breeding System
The MMRRC has always maintained this strain in a cryopreserved format. Information in the "Breeding", "Reproductive statistics" and "Special considerations" sections has been provided by the Donating Investigator
Breeding Scheme(s)

C57BL/6J female x Heterozygous male

Generation
N4 (C57BL/6)
Overall Breeding Performance
Poor
Viability and Fertility: Female Male Comments
Homozygotes are viable: Reduced Reduced Male and female homozygous mice die at ~ 3-6 months of age
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 4 months 4 months
Bred to Homozygosity
Yes
Average litter size
10
Recommended wean age
3 weeks
Average Pups Weaned
8

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
009966-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
009966-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
009966-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.