B6.Cg-Igf1r^tm1.1Mhz/Orl

Status	Available to order
EMMA ID	EM:15695
Citation information	RRID:IMSR_EM:15695 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information.
International strain name	B6.Cg-Igf1r^tm1.1Mhz/Orl
Alternative name	B6-Igf1rflox
Strain type	Targeted Mutant Strains : Conditional mutation
Allele/Transgene symbol	Igf1r^tm1.1Mhz
Gene/Transgene symbol	Igf1r

Information from provider

Provider	Martin HOLZENBERGER
Provider affiliation	Sorbonne Université INSERM, U938, Centre de recherche Saint Antoine
Genetic information	Mutants were generated by targeting the endogenous Igf1r (IGF type 1 receptor) gene with a replacement construct to flox the essential exon 3. The mutant Igf1r allele harbors 2 loxP sites flanking exon 3. This Igf1rflox strain is useful for generating conditional Igf1r gene knockout, for instance by crossing with mice that express cre recombinase.
Phenotypic information	Homozygous: Homozygous B6-Igf1r-flox mice show no phenotypic difference to wild-type C57BL/6, including growth, fertility and adult body weight. They are phenotypically strictly normal. Heterozygous: Heterozygous B6-Igf1r-flox mice show no phenotypic difference to wild-type C57BL/6.
Breeding history	This mutation was generated by homologous recombination, targeting the endogenous Igf1r gene with a replacement construct containing a floxed exon 3 and a floxed neomycin resistance cassette (tri-lox-construct). The selection cassette was subsequently eliminated in vivo by the cre recombinase deleter transgene EIIa-Cre. The resulting Igf1r-flox mutant devoid of the neo cassette was backcrossed to the C57BL/6J genetic background for more than 20 generations. Homozygous B6-Igf1r-flox mice were obtained by mating siblings. This strain is maintained since on C57BL/6 (B6) genetic background.
References	A targeted partial invalidation of the insulin-like growth factor I receptor gene in mice causes a postnatal growth deficit.;Holzenberger M, Leneuve P, Hamard G, Ducos B, Perin L, Binoux M, Le Bouc Y, ;2000;Endocrinology;141;2557-66; 10875258 Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene.;Holzenberger M, Lenzner C, Leneuve P, Zaoui R, Hamard G, Vaulont S, Bouc Y L, ;2000;Nucleic acids research;28;E92; 11058142 Experimental IGF-I receptor deficiency generates a sexually dimorphic pattern of organ-specific growth deficits in mice, affecting fat tissue in particular.;Holzenberger M, Hamard G, Zaoui R, Leneuve P, Ducos B, Beccavin C, Périn L, Le Bouc Y, ;2001;Endocrinology;142;4469-78; 11564712 Hepatocyte proliferation during liver regeneration is impaired in mice with liver-specific IGF-1R knockout.;Desbois-Mouthon Christèle, Wendum Dominique, Cadoret Axelle, Rey Colette, Leneuve Patricia, Blaise Annick, Housset Chantal, Tronche François, Le Bouc Yves, Holzenberger Martin, ;2006;FASEB journal : official publication of the Federation of American Societies for Experimental Biology;20;773-5; 16484330 Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.;Kappeler Laurent, De Magalhaes Filho Carlos, Dupont Joëlle, Leneuve Patricia, Cervera Pascale, Périn Laurence, Loudes Catherine, Blaise Annick, Klein Rüdiger, Epelbaum Jacques, Le Bouc Yves, Holzenberger Martin, ;2008;PLoS biology;6;e254; 18959478 Suppression of IGF-I signals in neural stem cells enhances neurogenesis and olfactory function during aging.;Chaker Zayna, Aïd Saba, Berry Hugues, Holzenberger Martin, ;2015;Aging cell;14;847-56; 26219530 Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.;Chaker Zayna, George Caroline, Petrovska Marija, Caron Jean-Baptiste, Lacube Philippe, Caillé Isabelle, Holzenberger Martin, ;2016;Neurobiology of aging;41;64-72; 27103519 Deleting IGF-1 receptor from forebrain neurons confers neuroprotection during stroke and upregulates endocrine somatotropin.;De Magalhaes Filho C Daniel, Kappeler Laurent, Dupont Joëlle, Solinc Julien, Villapol Sonia, Denis Cécile, Nosten-Bertrand Marika, Billard Jean-Marie, Blaise Annick, Tronche François, Giros Bruno, Charriaut-Marlangue Christiane, Aïd Saba, Le Bouc Yves, Holzenberger Martin, ;2017;Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism;37;396-412; 26762506 Disrupting IGF Signaling in Adult Mice Conditions Leanness, Resilient Energy Metabolism, and High Growth Hormone Pulses.;François Jean-Christophe, Aïd Saba, Chaker Zayna, Lacube Philippe, Xu Jie, Fayad Racha, Côté Francine, Even Patrick, Holzenberger Martin, ;2017;Endocrinology;158;2269-2283; 28881863 IGF-1R contributes to stress-induced hepatocellular damage in experimental cholestasis.;Cadoret Axelle, Rey Colette, Wendum Dominique, Elriz Khaldoun, Tronche François, Holzenberger Martin, Housset Chantal, ;2009;The American journal of pathology;175;627-35; 19628767
Homozygous fertile	yes
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	CNRS-TAAM – Typing and Archiving of Animal Models, Orléans, France
Animals used for archiving	homozygous C57BL/6J males

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

Growth delay due to insulin-like growth factor I resistance / Orphanet_73273

MGI phenotypes (gene matching)

abnormal cochlea morphology / MGI
abnormal lateral semicircular canal morphology / MGI
delayed bone ossification / MGI
abnormal hair follicle morphology / MGI
decreased hair follicle number / MGI
small hair follicles / MGI
abnormal liver morphology / MGI
muscle hypoplasia / MGI
decreased oligodendrocyte progenitor number / MGI
abnormal spinal cord morphology / MGI
atelectasis / MGI
translucent skin / MGI
thin epidermis / MGI
thin epidermis stratum spinosum / MGI
decreased body weight / MGI
cyanosis / MGI
postnatal growth retardation / MGI
respiratory failure / MGI
abnormal postnatal growth/weight/body size / MGI
abnormal muscle morphology / MGI
hydrops fetalis / MGI
abnormal semicircular canal morphology / MGI
abnormal posterior semicircular canal morphology / MGI
abnormal cochlear sensory epithelium morphology / MGI
abnormal bony labyrinth / MGI
abnormal cochlear inner hair cell morphology / MGI
decreased cochlear inner hair cell number / MGI
abnormal cochlear outer hair cell morphology / MGI
decreased cochlear outer hair cell number / MGI
decreased cochlear hair cell number / MGI
abnormal cochlear hair cell stereociliary bundle morphology / MGI
abnormal cochlear hair cell development / MGI
abnormal brainstem morphology / MGI
homeostasis/metabolism phenotype / MGI
growth/size/body region phenotype / MGI
decreased birth weight / MGI
prenatal growth retardation / MGI
abnormal inner hair cell kinocilium morphology / MGI
neonatal lethality, complete penetrance / MGI

Literature references

A targeted partial invalidation of the insulin-like growth factor I receptor gene in mice causes a postnatal growth deficit.;Holzenberger M, Leneuve P, Hamard G, Ducos B, Perin L, Binoux M, Le Bouc Y, ;2000;Endocrinology;141;2557-66; 10875258
Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene.;Holzenberger M, Lenzner C, Leneuve P, Zaoui R, Hamard G, Vaulont S, Bouc Y L, ;2000;Nucleic acids research;28;E92; 11058142
Experimental IGF-I receptor deficiency generates a sexually dimorphic pattern of organ-specific growth deficits in mice, affecting fat tissue in particular.;Holzenberger M, Hamard G, Zaoui R, Leneuve P, Ducos B, Beccavin C, Périn L, Le Bouc Y, ;2001;Endocrinology;142;4469-78; 11564712
Hepatocyte proliferation during liver regeneration is impaired in mice with liver-specific IGF-1R knockout.;Desbois-Mouthon Christèle, Wendum Dominique, Cadoret Axelle, Rey Colette, Leneuve Patricia, Blaise Annick, Housset Chantal, Tronche François, Le Bouc Yves, Holzenberger Martin, ;2006;FASEB journal : official publication of the Federation of American Societies for Experimental Biology;20;773-5; 16484330
Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.;Kappeler Laurent, De Magalhaes Filho Carlos, Dupont Joëlle, Leneuve Patricia, Cervera Pascale, Périn Laurence, Loudes Catherine, Blaise Annick, Klein Rüdiger, Epelbaum Jacques, Le Bouc Yves, Holzenberger Martin, ;2008;PLoS biology;6;e254; 18959478
Suppression of IGF-I signals in neural stem cells enhances neurogenesis and olfactory function during aging.;Chaker Zayna, Aïd Saba, Berry Hugues, Holzenberger Martin, ;2015;Aging cell;14;847-56; 26219530
Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.;Chaker Zayna, George Caroline, Petrovska Marija, Caron Jean-Baptiste, Lacube Philippe, Caillé Isabelle, Holzenberger Martin, ;2016;Neurobiology of aging;41;64-72; 27103519
Deleting IGF-1 receptor from forebrain neurons confers neuroprotection during stroke and upregulates endocrine somatotropin.;De Magalhaes Filho C Daniel, Kappeler Laurent, Dupont Joëlle, Solinc Julien, Villapol Sonia, Denis Cécile, Nosten-Bertrand Marika, Billard Jean-Marie, Blaise Annick, Tronche François, Giros Bruno, Charriaut-Marlangue Christiane, Aïd Saba, Le Bouc Yves, Holzenberger Martin, ;2017;Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism;37;396-412; 26762506
Disrupting IGF Signaling in Adult Mice Conditions Leanness, Resilient Energy Metabolism, and High Growth Hormone Pulses.;François Jean-Christophe, Aïd Saba, Chaker Zayna, Lacube Philippe, Xu Jie, Fayad Racha, Côté Francine, Even Patrick, Holzenberger Martin, ;2017;Endocrinology;158;2269-2283; 28881863
IGF-1R contributes to stress-induced hepatocellular damage in experimental cholestasis.;Cadoret Axelle, Rey Colette, Wendum Dominique, Elriz Khaldoun, Tronche François, Holzenberger Martin, Housset Chantal, ;2009;The American journal of pathology;175;627-35; 19628767

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Availabilities

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

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

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Practical information

Genotyping protocol

Example health report
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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.

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Legally binding conditions for the transfer

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B6.Cg-Igf1rtm1.1Mhz/Orl