This strain is used to model phases I to III of diabetes type II and obesity. Mice homozygous for the diabetes spontaneous mutation (Leprdb) manifest morbid obesity, chronic hyperglycemia, pancreatic beta cell atrophy and become hypoinsulinemic. Obesity starts at 3 to 4 weeks of age. Elevated plasma insulin begins at 10 to 14 days and elevated blood sugar at 4 to 8 weeks. Homozygous mice are polyphagic, polydipsic, and polyuric. The severity of disease on BKS background leads to uncontrolled rise in blood sugar, severe depletion of insulin-producing beta-cells of the pancreatic islets, peripheral neuropathy, myocardial disease and death by 10 months of age. Exogenous insulin fails to control blood glucose levels and gluconeogenic enzyme activity increases. Wound healing is delayed, and metabolic efficiency is increased.Read More +
This strain is maintained with Dock7m and Leprdb in repulsion. Although these genes are tightly linked, there is a small possibility of recombination. The heterozygotes we distribute are presumed to be non-recombinant, but are untested.
Mice homozygous for the diabetes spontaneous mutation (Leprdb) become identifiably obese around three to four weeks of age. Elevations of plasma insulin begin at 10 to 14 days of age and of blood sugar at four to eight weeks. Homozygous mutant mice are polyphagic, polydipsic, and polyuric. The course of the disease is markedly influenced by genetic background. A number of features are observed on the C57BLKS background, including an uncontrolled rise in blood sugar, severe depletion of the insulin-producing beta-cells of the pancreatic islets, and death by 10 months of age. Exogenous insulin fails to control blood glucose levels and gluconeogenic enzyme activity increases. Peripheral neuropathy and myocardial disease are seen in C57BLKS-Leprdb homozygotes. Wound healing is delayed, and metabolic efficiency is increased. Female homozygotes exhibit decreased uterine and ovarian weights, decreased ovarian hormone production and hypercytolipidemia in follicular granulosa and endometrial epithelial tissue layers (Garris et al., 2004, Garris et al., 2004).
Although normal in body weight, blood glucose, and plasma insulin, heterozygotes (Leprdb/+) also have increased metabolic efficiency and can survive a prolonged fast longer than controls. Experiments involving destruction of the ventromedial nucleus of the hypothalamus suggest that Leprdb may cause a defect in the hypothalamus. Steroid sulfotransferase enzymes, aberrantly expressed in diabetic mice, interact with the Leprdb mutation as modifiers of gender differences in obesity-induced diabetes susceptibility. Because of the sterility of Leprdb homozygotes, the misty (Dock7m) mutation has been incorporated into stocks for maintenance of the diabetes mutation. The repulsion double heterozygote (Dock7m +/+ Leprdb) facilitates identification of heterozygotes for breeding, while the coupling double heterozygote, (Dock7m Leprdb/+ +) allows identification of homozygotes before the phenotype becomes severe.
The recessive misty mutation causes a mild dilution of coat color and on certain backgrounds a white tail tip often accompanied by a belly spot. Melanocytes from Dock7m/Dock7m mice have a highly dendritic shape, show deficient proliferation in culture and have much more melanin content. Fewer melanoblasts are found in primary cultures from Dock7m/Dock7m mice than from wildtype controls. Between two and five weeks of age, Dock7m/Dock7m mice are smaller than controls. At 35 days of age they are shorter, weigh 15% less on average, and have less inguinal adipose mass than controls. Misty homozygotes completely lack brown fat. Although platelet count, seratonin content and ATP content are normal, Dock7m/Dock7m homozygotes have an increased bleed time and reduced platelet ADP levels.(Woolley 1941 and 1945; Truett et al. 1998; Sviderskaya et al. 1998.)
|Gene Symbol and Name||Dock7, dedicator of cytokinesis 7|
|Gene Synonym(s)||3110056M06Rik; 3110056M06Rik; EIEE23; Gm430; LOC242555; RIKEN cDNA 3110056M06 gene; ZIR2; gene model 430, (NCBI); m; m; mKIAA1771; misty|
|Strain of Origin||DBA/J|
|Molecular Note||Crosses between mice homozygous for misty and for moonlight, which mapped to overlapping critical regions on Chr 4, demonstrated failure of the two mutations to complement one another. Once moonlight had been identified as a mutation of Dock7 (Dock7mnlt), sequence analysis of this gene from misty mice revealed a retrotransposon LTR insertion following nucleotide 2045 (numbering from the A of the transcription initiation codon) that interrupts exon 18 and shifts the reading frame after codon 682 so that ten incorrect amino acids are incorporated into the protein before its premature termination.|
|Allele Synonym(s)||Lepdb; Lepr-; Leprdb-1J; db; db/db; leprdb|
|Gene Symbol and Name||Lepr, leptin receptor|
|Gene Synonym(s)||CD295; Fa; LEP-R; LEPRD; LEPROT; Leprb; Modb1; OB-R; OB-RGRP; OBR; Obr; db; diabetes; leptin receptor gene-related protein; obese-like; obese-like; obl; obl|
|Strain of Origin||C57BLKS/J|
|General Note|| |
Phenotypic Similarity to Human Syndrome: Gestational Diabetes J:219658
|Molecular Note||A G-to-T transversion in this allele created a donor splice site that causes abnormal splicing and a 106 nt insertion in the transcript, leading to premature termination of the long cellular domain of the Ob-Rb splice form and loss of its signal transducing function.|
Since both males and females homozygous for Leprdb are sterile, the closely linked coat color mutation, m, has been incorporated into stocks for maintenance of the db mutation. Breeding is performed by mating repulsion double heterozygotes, Dock7m +/+ Leprdb, which presumably yield 1/4 diabetics (black, obese at weaning) for studies , 1/2 wild-type repulsion double heterozygotes (black, lean) for futher breeding, and 1/4 misty mice (grey, lean) that can be discarded. The risk of recombination between the Dock7m and Leprdb loci is only about 2%, recognizable in pups as young as 3 days old by absence of pigment in paws and tip of tail. Dietary restrictions can prolong life and carbohydrate-free, protein-enriched defined diets can diminish the significantly the severity of the disease.
Wean-aged mice may show signs of barbering that include whisker picking. Affected mice typically regrow whiskers within two weeks after weaning.
|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.