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)|
|Allele Synonym(s)||targeted mutation 1, Valerie Lin; Ttc9tm1Vcl|
|Gene Symbol and Name||Ttc9, tetratricopeptide repeat domain 9|
|Gene Synonym(s)||RGD1565985; TTC9A; 1700029M07Rik; RIKEN cDNA 1700029M07 gene; AI853559; expressed sequence AI429215; expressed sequence AI853559; AI429215; 1700029M07Rik|
|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.
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