| Create Account | login

login

Strain

BKS.Cg-Dock7^m +/+ Lepr^db/J

Summary

Data Summary

Official Name	BKS.Cg-Dock7^m +/+ Lepr^db/J
Common Name	BKS db
Description	Dock7: 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. Lepr: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. 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 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. 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, misty has been incorporated into stocks for maintenance of the diabetes mutation. The repulsion double heterozygote (Leprdb +/+ Dock7m) facilitates identification of heterozygotes for breeding, while the coupling double heterozygote, (Leprdb Dock7m/+ +) allows identification of homozygotes before the onset of clinical symptoms.
Development Status	Phenotyping complete
Creation Method	spontaneous

Type	Count
Investigators	1
Genomics - Modifications	2
Experiments	14

Investigators

Name	Institution
Shengkan Jin	Robert Wood Johnson Medical School

Genomic Information

Gene	Allele 1	Allele 2	Protocol
Dock7	nucleotide insertion	nucleotide insertion	Not Specified
Lepr	point mutation - transversion	point mutation - transversion	Not Specified

OrderID	Order	Investigator	Experiment	Status	Measurements
13168	13168	Charles Giardina	Charles.Giardina.13168	Completed	40
30412	30412	Jin Shengkan	Circulating HbA1c levels in Lepr KO mice treated with derivatives of niclosamide	Completed	32
25850	25850	Jin Shengkan	Circulating insulin and HbA1c levels in Lepr KO mice treated with derivatives of niclosamide	Completed	38
26019	26019	Jin Shengkan	Circulating insulin and lipid levels in Lepr KO mice treated with niclosamide derivatives	Completed	324
25562	25562	Jin Shengkan	Circulating insulin, lipid, ALT, and AST levels in B6 mice treated with niclosamide	Completed	33
19619	19619	Jin Shengkan	Circulating lipid levels in BKS.Cg-m Lepr/+ + mice	Completed	152
30412	30412	Jin Shengkan	Circulating lipid, insulin, ALT and AST levels in Lepr KO mice treated with derivatives of niclosamide	Completed	384
10883	10883	Jin Shengkan	HbA1c levels in db/db KO mice treated with niclosamide	Completed	18
10905	10905	Shengkan Jin	HbA1c levels in db/db KO mice treated with niclosamide pt2	Completed	18
26019	26019	Jin Shengkan	HbA1c levels in Lepr KO mice treated with niclosamide derivatives	Completed	30
26125	26125	Jin Shengkan	Liver lipid levels in Lepr KO mice treated with derivatives of niclosamide	Completed	98
22006	22006	Xunshan Ding	Liver TG and TC levels in C57 mice treated with FGF-19	Completed	170
21978	21978	Jin Shengkan	Liver TG and TC measurements in BKS db KO mice	Completed	60
21958	21958	Zheng-Gen Jin	NEN CLAMS	Completed	480

Back to Top

Store Credentials?

MMPC-Live web resource – Terms of Use

Warranty disclaimer and copyright notice

THE MMPC-Live MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".

The Mouse Metabolic Phenotyping Centers (MMPC-Live) is an NIDDK funded consortium and adheres to the NIH Data Sharing Policy.

MMPC-Live clients make their data freely available whereby MMPC-Live users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC-Live using the following text: 'The MMPC-Live data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (MMPC-Live, RRID:SCR_008997, www.mmpc.org)'. To cite specific MMPC-Live centers, please use the appropriate RRID available from the MMPC-Live website (https://www.mmpc.org/shared/centers.aspx).

Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC-Live CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.

It is expected that MMPC-Live users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC-Live (such as summary data) and any plots, tables or screenshots depicting those data.

It is possible for invalid or incomplete results to be presented on the MMPC-Live web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.

Prohibited use. Data contributors and data users may not use MMPC-Live in any unlawful manner, or in any manner that could impair MMPC-Live services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.

MMPC-Live is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.

Menu

Home

Contact

About MMPC

Animal Husbandry

Tests Data

Search Data

Analysis

Clients

MMPC Centers

Newsletter

Interested in receiving MMPC News?

Mouse Phenotyping
@NationalMMPC

2017 National MMPC. All Rights Reserved.