Overview

Also Known As:Ttc9a^-, Ttc9a KO, TTC9AKO/Mmjax

Homozygous Ttc9 (tetratricopeptide repeat domain 9) knockout mice show enhanced mammary ductal branching and outgrowth upon steroid hormone administration as well as increased spleen and thymus mass and anxiety related behaviors. This strain may be useful for studying regulation of estrogen receptor alpha activity.

Donating Investigator

Valerie C Lin, Nanyang Technological University

Genetic overview

Genetic Background	Generation

Ttc9^tm1Vcl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ttc9	tetratricopeptide repeat domain 9

View Genetics

Research Applications

Neurobiology Research
Cell Biology Research
Endocrine Deficiency Research
Cancer Research
Internal/Organ Research

View All Research Applications

Details

Detailed Description

Ttc9 (tetratricopeptide repeat domain 9) is a chaperone protein involved in steroid receptor signaling. It is regulated by progesterone and estrogen and over-expressed in breast cancer cells. It carries three tetratricopeptide repeats (TPRs) that mediate protein interactions with Tpm3 (tropomyosin 3, gamma). Administration of 17-β-estradiol benzoate upregulates its expression in mammary gland and uterus. Widespread expression is seen in embryonic development as early as embryonic day E11.5, abundant expression in neural tissue is seen at E13.5. The protein is ubiquitously expressed in all tissues after birth; expression is highest in the brain and lowest in the liver.

This knockout strain carries a deletion of the first of the gene's three exons. The targeted allele expresses no protein or mRNA. Homozygotes are viable, fertile, and born at expected Mendelian ratios. Characterization of the female mice revealed that Ttc9a deficiency is associated with greater body weight, a bigger thymus, better mammary development and increased anxiety-like behavior. Furthermore, the Ttc9a-deficient mammary gland is more responsive to estrogen treatment with greater mammary ductal lengthening, ductal branching, and estrogen target gene induction. A significant increase in spleen mass is found in homozygous animals that are three weeks old. At six weeks of age, the mass of the thymus is significantly increased. The weight of the kidneys, heart, stomach, lungs, pancreas and uterus are comparable with wild type mice. This strain may be useful for studying regulation of estrogen receptor alpha activity as well as it's relation to anxiety-like behavior in female mice.

Development

Exon 1, encoding 70% of the protein, was replaced by a loxP-flanked neomycin resistance cassette. The targeting vector was injected into (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. The resulting chimeric animals were bred to C57BL/6J and offspring were backcrossed to C57BL/6 for at least 5 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lim LW; Shrestha S; Or YZ; Tan SZ; Chung HH; Sun Y; Lim CL; Khairuddin S; Lufkin T; Lin VC. 2016. Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice. Sci Rep 6:37568PubMed: 27869229 MGI: J:241702

View All References

Genetics

Ttc9^tm1Vcl

Allele Symbol: Ttc9^tm1Vcl

Allele Name	targeted mutation 1, Valerie Lin
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ttc9a^-
Gene Symbol and Name	Ttc9, tetratricopeptide repeat domain 9
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	12
Molecular Note	Exon 1, encoding 70% of the protein, was replaced by a loxP-flanked neomycin resistance cassette. Western blot and immunoblot analysis of brain, mammary gland, lung and uterus confirmed that no protein was expressed in mutant mice.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Behavioral and Learning Defects
  - high anxiety
Cell Biology Research
- Signal Transduction
Endocrine Deficiency Research
- Mammary Gland Defects
Cancer Research
- Growth Factors/Receptors/Cytokines
Internal/Organ Research
- Spleen Defects
- Thymus Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ttc9^tm1Vcl/Ttc9^tm1Vcl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

endocrine/exocrine gland phenotype

abnormal branching of the mammary ductal tree
- more ductal side branching and terminal end buds at age 6 weeks

increased thymus weight
- at age 6 weeks

thymus hyperplasia
- increment in mass from age 3 weeks to 6 weeks 58.5% versus 29.62% wild-type

immune system phenotype

increased spleen weight
- at age 6 weeks, significant at age 3 weeks

increased thymus weight
- at age 6 weeks

thymus hyperplasia
- increment in mass from age 3 weeks to 6 weeks 58.5% versus 29.62% wild-type

integument phenotype

abnormal branching of the mammary ductal tree
- more ductal side branching and terminal end buds at age 6 weeks

growth/size/body region phenotype

increased body weight
- 5-10% higher at all ages, significant at 6 and 10 weeks of age
- at age P2

increased spleen weight
- at age 6 weeks, significant at age 3 weeks

hematopoietic system phenotype

increased spleen weight
- at age 6 weeks, significant at age 3 weeks

increased thymus weight
- at age 6 weeks

thymus hyperplasia
- increment in mass from age 3 weeks to 6 weeks 58.5% versus 29.62% wild-type

Genotype: Ttc9^tm1Vcl/Ttc9⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

endocrine/exocrine gland phenotype

thymus hyperplasia
- increment in mass from age 3 weeks to 6 weeks 49.7% versus 29.62% wild-type

hematopoietic system phenotype

thymus hyperplasia
- increment in mass from age 3 weeks to 6 weeks 49.7% versus 29.62% wild-type

immune system phenotype

thymus hyperplasia
- increment in mass from age 3 weeks to 6 weeks 49.7% versus 29.62% wild-type

References

Lim LW; Shrestha S; Or YZ; Tan SZ; Chung HH; Sun Y; Lim CL; Khairuddin S; Lufkin T; Lin VC. 2016. Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice. Sci Rep 6:37568PubMed: 27869229 MGI: J:241702

Additional - Ttc9^tm1Vcl related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic Neo
- Standard PCR:Ttc9-alternate2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred by homozygote sibling matings.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the Ttc9a KO mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #43521 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Licensing Information

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Also Known As:Ttc9a-, Ttc9a KO, TTC9AKO/Mmjax

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ttc9tm1Vcl

Allele Symbol: Ttc9tm1Vcl

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Ttc9tm1Vcl/Ttc9tm1Vclinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6J

endocrine/exocrine gland phenotype

immune system phenotype

integument phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Ttc9tm1Vcl/Ttc9+involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

endocrine/exocrine gland phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Ttc9tm1Vcl related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Ttc9a^-, Ttc9a KO, TTC9AKO/Mmjax

Ttc9^tm1Vcl

Allele Symbol: Ttc9^tm1Vcl

Genotype: Ttc9^tm1Vcl/Ttc9^tm1Vcl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Genotype: Ttc9^tm1Vcl/Ttc9⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Additional - Ttc9^tm1Vcl related