B6.129S1(Cg)-Liftm1Stw/Cnbc

Status

Available to order

EMMA IDEM:02619
Citation informationRRID:IMSR_EM:02619 

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International strain nameB6.129S1(Cg)-Liftm1Stw/Cnbc
Alternative nameLif-KO
Strain typeTargeted Mutant Strains : Knock-out
Allele/Transgene symbolLiftm1Stw
Gene/Transgene symbolLif

Information from provider

ProviderJose Manuel Garcia Pichel
Provider affiliationIBMCC, CSIC
Genetic informationTargeting construct is derived from 129 DNA. Disruption caused by insertion of vector. A neomycin resistance gene was inserted into exon 3. Northern blot analysis on embryonic fibroblasts isolated from homozygous embryos demonstrated that no detectable transcript was produced from this allele, and cell growth assays confirmed that no functional protein was expressed from this allele. The original B6.129/Sv Lif mutants were outbred with different strains (BALB/c, MF1) for different purposes. Lately, in our animal facility they were backcrossed at least 8 times to the C57BL/6J background.
Phenotypic informationFemales lacking a functional LIF gene are fertile, but their blastocysts fail to implant and do not develop. The blastocysts, however, are viable and, when transferred to wild-type pseudopregnant recipients, they can implant and develop to term. Lif-deficient animals are growth retarded and they also show alterations in the nervous system, bone ossification, microvessel density, stem cell regeneration and in responses to stress and inflammation. In the present enriched C57BL/6 background, we noticed a high postnatal mortality (more than 60% die immediately after birth), and severe growth retardation in the Lif-deficient mice. Heterozygotes also show a mild growth deficiency.
Breeding historyThe original B6.129/Sv Lif mutants were outbred with different strains (BALB/c, MF1) for different purposes. Lately, in our animal facility they were backcrossed at least 8 times to the C57BL/6J background. Homozygous females do not implant embryos, therefore they can not be used in matings. In the present enriched C57BL/6 background some homozygous males are infertile. Heterozygous matings produce less embryos than normal mice. Optimal mating strategy to maintain the mutation is to mate heterozygous males with normal females.
References
  • Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.;Stewart C L, Kaspar P, Brunet L J, Bhatt H, Gadi I, Köntgen F, Abbondanzo S J, ;1992;Nature;359;76-9; 1522892
  • Murine leukemia inhibitory factor gene disruption attenuates the hypothalamo-pituitary-adrenal axis stress response.;Chesnokova V, Auernhammer C J, Melmed S, ;1998;Endocrinology;139;2209-16; 9564824
  • Leukemia inhibitory factor mediates the hypothalamic pituitary adrenal axis response to inflammation.;Chesnokova V, Melmed S, ;2000;Endocrinology;141;4032-40; 11089533
  • Leukemia inhibitory factor determines the growth status of injured adult sensory neurons.;Cafferty W B, Gardiner N J, Gavazzi I, Powell J, McMahon S B, Heath J K, Munson J, Cohen J, Thompson S W, ;2001;The Journal of neuroscience : the official journal of the Society for Neuroscience;21;7161-70; 11549727
  • Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model.;Holmberg Kristina H, Patterson Paul H, ;2006;Brain research;1075;26-35; 16458863
  • Leukemia inhibitory factor regulates microvessel density by modulating oxygen-dependent VEGF expression in mice.;Kubota Yoshiaki, Hirashima Masanori, Kishi Kazuo, Stewart Colin L, Suda Toshio, ;2008;The Journal of clinical investigation;118;2393-403; 18521186
  • Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia.;Bozec Aline, Bakiri Latifa, Hoebertz Astrid, Eferl Robert, Schilling Arndt F, Komnenovic Vukoslav, Scheuch Harald, Priemel Matthias, Stewart Colin L, Amling Michael, Wagner Erwin F, ;2008;Nature;454;221-5; 18548006
Homozygous fertileno
Homozygous viableyes
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreCNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain
Animals used for archivingheterozygous C57BL/6 males, wild-type C57BL/6OlaHsd females
Stage of embryos8-cell

Disease and phenotype information

MGI phenotypes (allele matching)
  • decreased motor neuron number / MGI
  • abnormal mammary gland physiology / MGI
  • decreased circulating adrenocorticotropin level / MGI
  • abnormal mammary gland growth during pregnancy / MGI
  • abnormal involution of the mammary gland / MGI
  • abnormal mammary gland duct morphology / MGI
  • abnormal mammary gland alveolus morphology / MGI
  • abnormal uterus morphology / MGI
  • decreased body weight / MGI
  • failure of embryo implantation / MGI
  • postnatal growth retardation / MGI
  • female infertility / MGI
  • abnormal CNS glial cell morphology / MGI
  • decreased body size / MGI
  • abnormal blood vessel morphology / MGI
  • abnormal astrocyte morphology / MGI
  • abnormal retinal vasculature morphology / MGI
  • nervous system phenotype / MGI
  • abnormal glial cell morphology / MGI
  • abnormal capillary morphology / MGI
  • abnormal brain vasculature morphology / MGI
  • increased acute inflammation / MGI
  • decreased susceptibility to injury / MGI
  • increased circulating interleukin-1 beta level / MGI
  • abnormal induced retinal neovascularization / MGI
  • increased vascular endothelial cell proliferation / MGI
  • decreased leukocyte cell number / MGI
  • abnormal hepatocyte morphology / MGI
  • tremors / MGI
  • abnormal pilomotor reflex / MGI
  • hepatic necrosis / MGI
  • increased circulating alanine transaminase level / MGI
  • thrombocytopenia / MGI
  • liver hemorrhage / MGI
  • diarrhea / MGI
  • increased circulating aspartate transaminase level / MGI
  • increased circulating tumor necrosis factor level / MGI
  • increased circulating interleukin-6 level / MGI
  • decreased interleukin-10 secretion / MGI
  • increased susceptibility to endotoxin shock / MGI
  • increased susceptibility to bacterial infection induced morbidity/mortality / MGI
  • liver vascular congestion / MGI
  • increased susceptibility to weight loss / MGI
  • abnormal circulating serum amyloid protein level / MGI
  • abnormal skeleton morphology / MGI
  • postnatal lethality, incomplete penetrance / MGI
  • decreased circulating triglyceride level / MGI
  • increased circulating insulin-like growth factor I level / MGI
  • increased circulating leptin level / MGI
  • abnormal osteoclast physiology / MGI
  • abnormal osteoclast morphology / MGI
  • increased osteoclast cell number / MGI
  • increased bone resorption / MGI
  • hypoxia / MGI
  • abnormal osteoclast differentiation / MGI
  • decreased bone volume / MGI
MGI phenotypes (gene matching)
  • decreased leukocyte cell number / MGI
  • abnormal hepatocyte morphology / MGI
  • tremors / MGI
  • decreased motor neuron number / MGI
  • abnormal CNS glial cell morphology / MGI
  • abnormal uterus morphology / MGI
  • decreased body weight / MGI
  • decreased body size / MGI
  • abnormal pilomotor reflex / MGI
  • abnormal osteoclast physiology / MGI
  • abnormal blood vessel morphology / MGI
  • hepatic necrosis / MGI
  • failure of embryo implantation / MGI
  • postnatal growth retardation / MGI
  • abnormal mammary gland physiology / MGI
  • female infertility / MGI
  • abnormal astrocyte morphology / MGI
  • abnormal macrophage morphology / MGI
  • decreased circulating triglyceride level / MGI
  • decreased circulating adrenocorticotropin level / MGI
  • abnormal retinal vasculature morphology / MGI
  • increased circulating alanine transaminase level / MGI
  • thrombocytopenia / MGI
  • nervous system phenotype / MGI
  • abnormal glial cell morphology / MGI
  • abnormal capillary morphology / MGI
  • liver hemorrhage / MGI
  • increased circulating insulin-like growth factor I level / MGI
  • decreased hematopoietic stem cell number / MGI
  • abnormal brain vasculature morphology / MGI
  • abnormal osteoclast morphology / MGI
  • increased osteoclast cell number / MGI
  • increased bone resorption / MGI
  • increased eosinophil cell number / MGI
  • diarrhea / MGI
  • hypoxia / MGI
  • increased acute inflammation / MGI
  • decreased T cell proliferation / MGI
  • decreased susceptibility to injury / MGI
  • increased circulating aspartate transaminase level / MGI
  • hematopoietic system phenotype / MGI
  • abnormal skeleton morphology / MGI
  • increased circulating leptin level / MGI
  • abnormal mammary gland growth during pregnancy / MGI
  • abnormal involution of the mammary gland / MGI
  • abnormal osteoclast differentiation / MGI
  • increased circulating tumor necrosis factor level / MGI
  • increased circulating interleukin-6 level / MGI
  • increased circulating interleukin-1 beta level / MGI
  • decreased interleukin-10 secretion / MGI
  • increased susceptibility to endotoxin shock / MGI
  • decreased common myeloid progenitor cell number / MGI
  • decreased erythroid progenitor cell number / MGI
  • increased uterine NK cell number / MGI
  • abnormal mammary gland duct morphology / MGI
  • abnormal mammary gland alveolus morphology / MGI
  • abnormal induced retinal neovascularization / MGI
  • abnormal uterine receptivity / MGI
  • abnormal embryo apposition / MGI
  • abnormal embryo attachment / MGI
  • increased susceptibility to bacterial infection induced morbidity/mortality / MGI
  • liver vascular congestion / MGI
  • increased susceptibility to weight loss / MGI
  • abnormal circulating serum amyloid protein level / MGI
  • decreased bone volume / MGI
  • postnatal lethality, incomplete penetrance / MGI
  • increased vascular endothelial cell proliferation / MGI

Literature references

  • Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.;Stewart C L, Kaspar P, Brunet L J, Bhatt H, Gadi I, Köntgen F, Abbondanzo S J, ;1992;Nature;359;76-9; 1522892
  • Murine leukemia inhibitory factor gene disruption attenuates the hypothalamo-pituitary-adrenal axis stress response.;Chesnokova V, Auernhammer C J, Melmed S, ;1998;Endocrinology;139;2209-16; 9564824
  • Leukemia inhibitory factor mediates the hypothalamic pituitary adrenal axis response to inflammation.;Chesnokova V, Melmed S, ;2000;Endocrinology;141;4032-40; 11089533
  • Leukemia inhibitory factor determines the growth status of injured adult sensory neurons.;Cafferty W B, Gardiner N J, Gavazzi I, Powell J, McMahon S B, Heath J K, Munson J, Cohen J, Thompson S W, ;2001;The Journal of neuroscience : the official journal of the Society for Neuroscience;21;7161-70; 11549727
  • Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model.;Holmberg Kristina H, Patterson Paul H, ;2006;Brain research;1075;26-35; 16458863
  • Leukemia inhibitory factor regulates microvessel density by modulating oxygen-dependent VEGF expression in mice.;Kubota Yoshiaki, Hirashima Masanori, Kishi Kazuo, Stewart Colin L, Suda Toshio, ;2008;The Journal of clinical investigation;118;2393-403; 18521186
  • Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia.;Bozec Aline, Bakiri Latifa, Hoebertz Astrid, Eferl Robert, Schilling Arndt F, Komnenovic Vukoslav, Scheuch Harald, Priemel Matthias, Stewart Colin L, Amling Michael, Wagner Erwin F, ;2008;Nature;454;221-5; 18548006
  • Leukemia inhibitory factor protects against experimental periodontitis through immuno-modulations of both macrophages and periodontal ligament fibroblasts.;Ou Yanjing, Fan Le, Wang Xiaoqi, Xia Haibin, Cheng Mengwen, Huang Jing, Liang Youde, Wang Yining, Zhou Yi, ;2024;Journal of periodontology;95;1073-1085; 38488753

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