STOCK Tnfrsf1a^tm1Blt Tg(Gfap-TNF*)K21Gkl/Flmg

Status	Available to order
EMMA ID	EM:08444
International strain name	STOCK Tnfrsf1a^tm1Blt Tg(Gfap-TNF*)K21Gkl/Flmg
Alternative name	TgK21 [CBA;B6-Tnfrsf1a Tg(Gfap-TNF*)K21Gkl/Flmg]
Strain type	Transgenic Strains
Allele/Transgene symbol	Tg(Gfap-TNF*)K21Gkl, Tnfrsf1a^tm1Blt
Gene/Transgene symbol	Tg(Gfap-TNF*)K21Gkl, Tnfrsf1a

Information from provider

Provider	George Kollias
Provider affiliation	Immunology, BSRC Al. Fleming
Genetic information	The -2663 to +93 region of the murine Gfap promoter, which has been shown to contain cis-regulatory elements required for astrocyte-specific expression, was fused to human TNF genomic sequences containing a deletion mutation of the codons encoding the 1st to the 12th amino acids of the mature 17-kDa TNF protein. This mutant TNF gene has previously been shown to produce a transmembrane TNF protein that remains bioactive against cellular targets in vitro and in vivo. The genomic DNA was then ligated to the 0.77-kb EcoRI-Sal1 fragment containing the 3' UTR and polyadenylation site of the beta-globin gene, which replaces TNF 3' UTR sequences, thought to negatively regulate mRNA stability and translational efficiency. In this transgenic line, exogenous TNF protein production could be demonstrated by positive immunostaining of astrocytes in the spinal cord and brain sections using a polyclonal anti-human TNF antiserum.
Phenotypic information	Homozygous: n/a Heterozygous: Neurologic disorder manifested by ataxia, seizures, and paralysis and bearing histologic evidence of chronic CNS inflammation and degeneration; 100% phenotypic penetrance.
References	Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice.;Akassoglou K, Probert L, Kontogeorgos G, Kollias G, ;1997;Journal of immunology (Baltimore, Md. : 1950);158;438-45; 8977220 Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy.;Akassoglou K, Bauer J, Kassiotis G, Pasparakis M, Lassmann H, Kollias G, Probert L, ;1998;The American journal of pathology;153;801-13; 9736029
Homozygous fertile	no
Homozygous viable	no
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	B.S.R.C. Alexander Fleming, Vari, Greece
Animals used for archiving	heterozygous CBA x C57BL/6, wild-type (CBA x C57BL/6)F1
Stage of embryos	Morula

Disease and phenotype information

MGI allele-associated human disease models

multiple sclerosis / DOID:2377

Orphanet associated rare diseases, based on orthologous gene matching

Tumor necrosis factor receptor 1 associated periodic syndrome / Orphanet_32960

IMPC phenotypes (gene matching)

abnormal skin morphology / IMPC
increased large unstained cell number / IMPC
increased grip strength / IMPC
increased basophil cell number / IMPC
increased neutrophil cell number / IMPC
increased eosinophil cell number / IMPC
increased NK cell number / IMPC
abnormal cholesterol homeostasis / IMPC
decreased circulating calcium level / IMPC
increased lymphocyte cell number / IMPC
increased effector memory CD8-positive, alpha-beta T cell number / IMPC
increased circulating aspartate transaminase level / IMPC
enlarged heart / IMPC
increased leukocyte cell number / IMPC
decreased monocyte cell number / IMPC
abnormal heart morphology / IMPC
decreased neutrophil cell number / IMPC

MGI phenotypes (allele matching)

abnormal response/metabolism to endogenous compounds / MGI
decreased circulating interleukin-6 level / MGI
decreased sensitivity to induced morbidity/mortality / MGI
decreased physiological sensitivity to xenobiotic / MGI
decreased sensitivity to xenobiotic induced morbidity/mortality / MGI
abnormal sleep pattern / MGI
impaired central nervous system regeneration / MGI
increased sensitivity to induced cell death / MGI
increased susceptibility to bacterial infection induced morbidity/mortality / MGI
impaired humoral immune response / MGI
decreased susceptibility to bacterial infection / MGI
decreased circulating alanine transaminase level / MGI
abnormal Peyer's patch morphology / MGI
abnormal immune system physiology / MGI
abnormal lymph node B cell domain morphology / MGI
abnormal Peyer's patch follicle morphology / MGI
increased susceptibility to bacterial infection / MGI
decreased susceptibility to experimental autoimmune encephalomyelitis / MGI
increased susceptibility to parasitic infection / MGI
increased susceptibility to type I hypersensitivity reaction / MGI
decreased Peyer's patch number / MGI
absent follicular dendritic cells / MGI
decreased IgG1 level / MGI
decreased interleukin-6 secretion / MGI

MGI phenotypes (gene matching)

increased bone mineral density / MGI
abnormal Peyer's patch morphology / MGI
abnormal sleep pattern / MGI
abnormal immune system physiology / MGI
decreased IgG level / MGI
liver inflammation / MGI
lung inflammation / MGI
decreased inflammatory response / MGI
increased skin papilloma incidence / MGI
decreased tumor incidence / MGI
abnormal respiratory mechanics / MGI
abnormal airway responsiveness / MGI
abnormal lymph node B cell domain morphology / MGI
abnormal spleen germinal center morphology / MGI
abnormal Peyer's patch follicle morphology / MGI
decreased susceptibility to bacterial infection / MGI
increased susceptibility to bacterial infection / MGI
abnormal macrophage physiology / MGI
granulomatous inflammation / MGI
impaired skin barrier function / MGI
abnormal glutamate-mediated receptor currents / MGI
decreased circulating alanine transaminase level / MGI
abnormal cytokine secretion / MGI
no phenotypic analysis / MGI
abnormal nervous system physiology / MGI
abnormal response/metabolism to endogenous compounds / MGI
increased susceptibility to experimental autoimmune encephalomyelitis / MGI
decreased susceptibility to experimental autoimmune encephalomyelitis / MGI
decreased susceptibility to autoimmune diabetes / MGI
increased susceptibility to parasitic infection / MGI
increased susceptibility to type I hypersensitivity reaction / MGI
decreased Peyer's patch number / MGI
abnormal follicular dendritic cell morphology / MGI
absent follicular dendritic cells / MGI
decreased IgG1 level / MGI
increased circulating tumor necrosis factor level / MGI
decreased circulating interleukin-6 level / MGI
decreased circulating interleukin-1 beta level / MGI
increased interleukin-6 secretion / MGI
decreased interleukin-6 secretion / MGI
abnormal chemokine secretion / MGI
decreased susceptibility to endotoxin shock / MGI
increased susceptibility to endotoxin shock / MGI
decreased physiological sensitivity to xenobiotic / MGI
increased sensitivity to induced cell death / MGI
increased sensitivity to induced morbidity/mortality / MGI
decreased sensitivity to induced morbidity/mortality / MGI
decreased sensitivity to xenobiotic induced morbidity/mortality / MGI
increased susceptibility to bacterial infection induced morbidity/mortality / MGI
abnormal neuron proliferation / MGI
abnormal oval cell physiology / MGI
tumor regression / MGI
impaired adaptive thermogenesis / MGI
decreased susceptibility to dopaminergic neuron neurotoxicity / MGI
decreased microglial cell number / MGI
impaired humoral immune response / MGI
impaired central nervous system regeneration / MGI

Literature references

Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice.;Akassoglou K, Probert L, Kontogeorgos G, Kollias G, ;1997;Journal of immunology (Baltimore, Md. : 1950);158;438-45; 8977220
Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy.;Akassoglou K, Bauer J, Kassiotis G, Pasparakis M, Lassmann H, Kollias G, Probert L, ;1998;The American journal of pathology;153;801-13; 9736029

Information on how we integrate external resources can be found here

Order

Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740^*
Rederivation of mice from frozen stock, delivery time available upon request . €3880^*

Due to the dynamic nature of our processes strain availability may change at short notice. The local repository manager will advise you in these circumstances.

^* In addition users have to cover all the shipping costs (including the cost for returning dry-shippers, where applicable).

More details on pricing and delivery times

Practical information

Genotyping protocol

Example health report
(Current health report will be provided later)

Material Transfer Agreement (MTA)
Distribution of this strain is subject to a provider MTA. Both signing of the MTA and submission of the online EMMA Mutant Request Form are required before material can be shipped.

EMMA conditions
Legally binding conditions for the transfer

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STOCK Tnfrsf1atm1Blt Tg(Gfap-TNF*)K21Gkl/Flmg