These mice express Let-7S21L (let-7g (Mirlet7g) Stem, mir-21 (Mir21) Loop) under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter and are useful in studies of growth and metabolism.
George Q. Daley, Children's Hospital BostonRead More +
Lin28a (lin-28 homolog A (C. elegans)) and Lin28b (lin-28 homolog B (C. elegans)) encode RNA-binding proteins that block the biogenesis of Mirlet7 (let-7) microRNAs. Let-7 targets are known regulators of mammalian body size and metabolism.
This strain was constructed to determine whether altered let-7 expression might produce phenotypes opposite those of strains over-expressing Lin28a (see Stock No. 023910) or Lin28b (see Stock No. 0023911). It expresses Let-7S21L (let-7g Stem, mir-21 Loop) under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter. Let-7S21L represents a chimeric Mirlet7g (microRNA let7g) stem/Mir21 (microRNA 21) loop fusion that cannot bind LIN28, thus allowing for let-7 processing despite Lin28 expression. This ensures that endogenous LIN28 cannot block pri- or pre-let-7g biosynthesis.
Mirlet7g/Mir21 expression can be regulated in progeny derived from crosses with rtTA or tTA mice. When crossed with Gt(ROSA)26Sor M2-rtTA strain (see Stock No. 006965), uninduced male mice exhibit no leakiness of expression and exhibit no growth or glucose phenotypes. Widespread induction from three weeks of age onward increases mature MIRLET7G levels in liver (>50-fold), skin (>20-fold), fat (approximately 4-fold) and muscle (approximately 4-fold). Induced animals show reduced body size and growth rates. After 5 days of induction, mice produce an increase in fed state glucose. Glucose tolerance testing reveals glucose intolerance in mice fed either a normal or high fat diet. Insulin tolerance testing fails to detect a difference in insulin sensitivity. Mutant mice produce more insulin than control mice.
A targeting vector containing a splice acceptor, 2 polyadenylation sequences, a tetracycline operator, let-7S21L, and an SV40 polyadenylation signal within 3'UTR of the mouse Col1a1 gene was introduced to (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells containing M2-rtTA (optimized rtTA) targeted to the Gt(ROSA)26Sor locus promoter (see Stock No. 006965 for mutation details). Let-7S21L (let-7g Stem, mir-21 Loop) represents a chimeric Mirlet7g (microRNA let7g) stem/Mir21 (microRNA 21) loop fusion. Resultant chimeric males were crossed with outbred CD1 females. The Gt(ROSA)26Sor M2-rtTA mutation was bred away from this strain. The line was backcrossed to C57BL/6 for 8 generations by the donating lab.
|Allele Name||targeted mutation 3, George Q Daley|
|Allele Type||Targeted (Inducible, Inserted expressed sequence, Recombinase-mediated cassette exchange-ready)|
|Allele Synonym(s)||iLet-7; let-7; let-7S21L|
|Gene Symbol and Name||Col1a1, collagen, type I, alpha 1|
|Gene Synonym(s)||COLIA1; Col1a-1; Col1a-1; Cola-1; Cola-1; Cola1; Cola1; EDSC; Moloney leukemia virus 13; Mov-13; Mov-13; OI1; OI2; OI3; OI4|
|Promoter||tetO, tet operator,|
|Strain of Origin||(C57BL/6 x 129S4/SvJae)F1|
|General Note||The allele was made in KH2 cells that carry Gt(ROSA)26Sortm1(rtTA*M2)Jae and Col1a1tm13(neo/hygro*)Jae.|
|Molecular Note||RMCE on KH2 cells inserted a cassette that contains a splice acceptor, 2 polyadenylation sequence, tetracycline operator, a fusion of the Mirlet7g stem sequence and the Mir21 loop sequence, and an SV40 polyadenylation signal into the 3'UTR. No expressionof the inserted sequence is detected in the absence of doxycycline treatment.|
Homozygous and heterozygous mice are viable and fertile.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"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.