Homozygous Mark2 (MAP/microtubule affinity-regulating kinase 2) targeted mice show and increased metabolic rate, decreased adiposity, resistance to high fat diet-induced weight gain, and insulin hypersensitivity. Approximately 85% of homozygotes exhibit some combination of immunological disorders between the ages of 5 and 12 months. Aging animals (~6-7 months) develop splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Roughly 30% of homozygotes present colorectal prolapse that is more severe in females than males after the age of 5 months. This strain may be useful in studies of immune system homeostasis, autoimmune disease, obesity, and diabetes.
Dr. Helen Piwnica-Worms, MD Anderson Cancer Center
Homozygous targeted mice show and increased metabolic rate, decreased adiposity, resistance to high fat diet-induced weight gain, and insulin hypersensitivity. Western blot analysis demonstrates that expression is eliminated in brain, spleen, kidney and liver, lymph nodes, thymus, white and brown adipose tissues, large and small intestines, stomach. Homozygous pups are born slightly below predicted Mendelian ratios and show both embryonic and postnatal growth retardation as well as increased mortality as compared to wildtype animals. The age of death can range from 3 weeks to several months. Approximately 85% of homozygotes exhibit some combination of immunological disorders between the ages of 5 and 12 months. B and T cell development is normal, but CD4+ T cells lacking this protein exhibit a marked upregulation of the memory marker CD44 and produce more gamma interferon and interleukin 4 on stimulation through the T cell receptor in vitro. B cell responses to T cell-dependent and -independent antigen challenge are altered in vivo. Aging animals (~6-7 months) develop splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Roughly 30% of homozygotes present colorectal prolapse that is more severe in females than males after the age of 5 months. This strain may be useful in studies of immune system homeostasis, autoimmune disease, obesity, and diabetes.
A portion of exon 2 and all of exons 3 and 4 were replaced by a selection cassette containing the neomycin phosphotransferase cDNA flanked 5' by the thymidine kinase promoter and 3' by the thymidine kinase polyadenylation sequence. The mutation was created using 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Male chimeras were bred to C57BL/6 females. The line was backcrossed 18 times to C57BL/6 by the donating laboratory.
|Allele Name||targeted mutation 1, Helen Piwnica-Worms|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Enk-; Mark2/EMK-; Par-1b-|
|Gene Symbol and Name||Mark2, MAP/microtubule affinity regulating kinase 2|
|Gene Synonym(s)||AU024026; ELKL motif kinase; EMK-1; EMK1; Emk; Emk; PAR-1; Par-1; Par-1b; Par1b; expressed sequence AU024026|
|Strain of Origin||129X1/SvJ|
|Molecular Note||The insertion of a neomycin selection cassette deleted sequence from exons 2, 3, and 4. The replaced region encoded residues of the glycine-rich motif involved in MgATP-binding. Western blot analysis of extracts from fibroblasts showed an absence of all known isoforms produced from the targeted allele in homozygous mutant embryos. Immunoprecipitates of tissue extracts derived from homozygous mutant mice failed to phosphorylate GST-Cdc25C in vitro, incdicating ablation of kinase activity.|
|Mutations Made By|| |
Dr. Helen Piwnica-Worms, MD Anderson Cancer Center
When maintained as a live colony, heterozygotes may be bred. Homozygotes, although fertile, are somewhat small and females have problems with gestation and lactation; their litter sizes when bred to wildtype males are smaller than normal.
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
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