Beginning around six months of age, these Mll-AF9 knock-in mice recapitulate the acute myeloid leukemia (AML) phenotype associated with the t(9;11)(p22;q23) translocation in humans and may be useful for studying hematopoietic development, cancer, and acute myeloid leukemia.
John H Kersey, Masonic Cancer Center (Univ of Minn)
These Mll-AF9 knock-in mice are on a mixed genetic background (C57BL/6, 129P and possibly other contributions). It should be noted that their phenotype could vary from that originally published. We may modify the strain description if necessary as published results become available. The published phenotype is described below:
The Mll-AF9 knock-in allele encodes a MLL-AF9 fusion protein that mimics the t(9;11)(p22;q23) translocation identified in acute myeloid leukemia (AML) patients. While homozygous mice are not viable, heterozygotes are viable and fertile but females are poor mothers and may not survive pregnancy. Expression of the MLL-AF9 fusion protein results in development of leukemia beginning around six months of age; almost all of which are AMLs. Detectable proliferation of myeloid cells is observed in bone marrow by as little as six days after birth, and this early accumulation of myeloid precursors likely confers a greater chance of acquiring secondary mutations that cooperate in the appearance of overt cancer. These Mll-AF9 knock-in mice may be useful for studying hematopoietic development, cancer, and AML. As of 2014, our Mll-AF9 knock-in colony exhibits several coat colors including black, agouti and tan.
These Mll-AF9 knock-in mice were generated in the laboratory of Dr. Terence H Rabbitts (Medical Research Council Laboratory of Molecular Biology, Cambridge UK and currently Leeds Institute of Molecular Medicine, Leeds UK). A targeting vector was used for in-frame fusion of a 3'-terminal human AF9 cDNA sequence (nucleotide 1634 to the translation terminus of the MLLT3 locus) and an SV40 poly(A) signal into the BamHI site of exon 8 (corresponding to nucleotide 3987) of the targeted gene. This also inserted a MC1-neo-poly(A) cassette immediately downstream of the fusion segment. The targeting construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6 and/or wildtype siblings and/or outbred MF1 females. Mll-AF9 knock-in mice were subsequently bred with C57BL/6 mice for an unknown number of generations and then sent to the laboratory of Dr. John H Kersey (Masonic Cancer Center, University of Minnesota). There, the mutant males were bred with C57BL/6NCrl females for four generations, and next maintained by breeding mutant males with wildtype female siblings for approximately 20 generations prior to arrival at The Jackson Laboratory. The donating investigator reports both agouti and black coat colors (see SNP note below). In 2010, agouti males and black males were sent to The Jackson Laboratory Repository. Upon arrival, sperm was frozen. An aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6NJ (Stock No. 005304). Until 2012, The Jackson Laboratory Repository colony was maintained by breeding heterozygous males with wildtype females from the colony or C57BL/6NJ females. Beginning in 2012, in an attempt to improve breeding performance, The Jackson Laboratory Repository will maintain the live colony by breeding heterozygous males with wildtype females from the colony or B6129PF1/J females (Stock No. 100492).
In 2011, a 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the living colony rederived using C57BL/6NJ at The Jackson Laboratory Repository. At least 3 markers are segregating, suggesting an incomplete backcross. Also, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.
|Expressed Gene||MLLT3, MLLT3, super elongation complex subunit, human|
|Site of Expression|
|Allele Name||targeted mutation 2, Terence H Rabbitts|
|Allele Type||Targeted (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||Mllaf9; Mll1tm2Thr; Mll-AF9+|
|Gene Symbol and Name||Kmt2a, lysine (K)-specific methyltransferase 2A|
|Expressed Gene||MLLT3, MLLT3, super elongation complex subunit, human|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Sequence encoding a 3' portion of human MLLT3 extending from nucleotide 1634 to the translation terminus replaced a 3' portion of murine Kmt2a exon 8. A downstream neo cassette was also included in the targeting vector for selection. The resultant fusion product putatively recapitulates the KMT2A(MLL)/MLLT3 protein produced in patients with the acute myeloid leukamia (AML) associated transloaction T(9;11)(p22;q23).|
|Mutations Made By|| |
Terence Rabbitts, Leeds Institute of Molecular Med (LIMM)
Until 2012, The Jackson Laboratory Repository colony was maintained by breeding heterozygous males with wildtype females from the colony or C57BL/6NJ females. Beginning in 2012, in an attempt to improve breeding performance, The Jackson Laboratory Repository will maintain the live colony by breeding heterozygous males with wildtype females from the colony or B6129PF1/J females (Stock No. 100492). Homozygous mice are not viable and heterozygous females are poor mothers and may not survive pregnancy. As of 2014, our Mll-AF9 knock-in colony exhibits several coat colors including black, agouti and tan.
When using the Mll-AF9 mouse strain in a publication, please cite the originating article(s) and include JAX stock #009079 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.