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.
Valerie C Lin, Nanyang Technological University
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.
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.
|Allele Name||targeted mutation 1, Valerie Lin|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ttc9, tetratricopeptide repeat domain 9|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|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.|
When maintaining a live colony, these mice are bred by homozygote sibling matings.
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.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.