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An FRT flanked gene trap cassette with a lacZ reporter and a splice acceptor was inserted via homologous recombination between exons 1 and 2, disrupting the gene. Additionally, loxP cassettes were inserted flanking exons 2 through 8 rendering this a conditional-ready allele.
Genotyping Protocol
Conditional phenotype: Not determined.
Homozygous deletion of C1qtnf12 gene results in sexually dimorphic phenotypes. Under basal conditions, complete loss of C1qtnf12 gene product (a.k.a. CTRP12) improved insulin sensitivity in female mice. When challenged with a high-fat diet, C1qtnf12 knockout (KO) male mice had decreased energy expenditure, increased weight gain and adiposity, elevated serum TNFα level, and reduced insulin sensitivity. In contrast, female KO mice had reduced weight gain and liver weight. C1qtnf12 KO male mice fed an obesogenic diet also had lower circulating triglyceride and free fatty acid levels.
In C1qtnf12(+/-) heterozygous male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, C1qtnf12(+/-) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. When obesity was induced by high-fat feeding, C1qtnf12(+/-) heterozygous female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in C1qtnf12(+/-) female mice fed a high-fat diet.
A construct was generated by the Mouse Biology Program similar to a KOMP knockout-first allele. The vector was electroporated into JM8A3.N1 ES cells (C57BL/6N), and three mutant clones that passed screening and were injected into blastocysts. The resulting chimeras were mated to C57BL/6NTac females, and germline mice were assessed for containing the correct allele. Heterozygous knockout-first males and C57BL/6NTac females were used for sperm and embryo cryopreservation.
Tan SY, Little HC, Lei X, Li S, Rodriguez S, Wong GW. Partial deficiency of CTRP12 alters hepatic lipid metabolism. Physiol Genomics. 2016 Dec 1;48(12):936-949. doi: 10.1152/physiolgenomics.00111.2016. Epub 2016 Nov 4. (Medline PMID: 27815536)
Tan SY, Lei X, Little HC, Rodriguez S, Sarver DC, Cao X, Wong GW. CTRP12 ablation differentially affects energy expenditure, body weight, and insulin sensitivity in male and female mice. Am J Physiol Endocrinol Metab. 2020 Jul 1;319(1):E146-E162. doi: 10.1152/ajpendo.00533.2019. Epub 2020 May 18. (Medline PMID: 32421370)
Colony Surveillance Program and Current Health Reports
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.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Jeanine Pennington.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Jeanine Pennington
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.
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.
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.