C57BL/6-Rag2em1Bdes Csf1em1(CSF1)Bdes/Ph

Status

Under development - register interest

EMMA IDEM:15928
Citation informationRRID:IMSR_EM:15928 

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 nameC57BL/6-Rag2em1Bdes Csf1em1(CSF1)Bdes/Ph
Alternative namehCsf1Bdes (Csf1em1(CSF1)Bdes;Rag2em1Bdes)
Strain typeEndonuclease-mediated
Allele/Transgene symbolRag2em1Bdes, Csf1em1(CSF1)Bdes
Gene/Transgene symbolRag2, Csf1

Information from provider

ProviderBart De Strooper
Provider affiliationKU Leuven and VIB
Genetic informationHumanisation of the Csf1 gene by endonuclease mediated gene targeting. Knock-out of the Rag2 gene by endonuclease mediated gene targeting. The Csf1em1(CSF1)Bdes;Rag2em1Bdes (short name: hCsf1Bdes) double-mutant mouse strain facilitates the use of the xenotransplantation paradigm for human microglia to study complex human disease.
Phenotypic informationHomozygous:
Mice are lacking T and B cells (immune deficient) and express human CSF1, which make make them suitable for xenografting human microglia.

Heterozygous:
no abnormal phenotype
Breeding historyCRISPR/Cas9 technology was used to replace the genomic DNA sequence corresponding to amino acid 33–552 of the mouse Csf1 gene with the human CSF1 genomic sequence corresponding to amino acid 33–554 in the endogenous gene. The 5’ murine signal peptide (amino acid 1–32) and 3’ region of the mouse were retained. The gRNAs (target sequence ACA GTG TTC TGA CAC CTC CTTGG and GTG GAA CTG CCA GTA TAG AAAGG ) to the mouse Csf1 gene, the donor vector (PCR assembled from BAC: RP23-15F10 (mouse) and BAC: RP11-101M23 (human)), and Cas9 mRNA were co-injected into fertilized mouse eggs of C57BL/6J mice. F0 founder animals were identified by extensive PCR analysis followed by Sanger sequence analysis. F0 were bred to wild-type mice to test germline transmission and generate F1 animals. F1 animals were backcrossed to wild-type mice to generate F2. This line is called Csf1em1(CSF1)Bdes. Rag2em1Bdes knock-out: CRISPR/Cas9 technology (target sequence AAC ATA GCC TTA ATT CAA CCAGG and ACG AGT CTG TAA CCG GCT ACTGG and Cas9 enzyme obtained from IDT) was used to generate an F0 founder in C57BL/6J mice. The F0 founder was selected by extensive analysis utilizing PCR and sequencing which demonstrated a 1198 bp genomic DNA deletion which corresponds to amino acid 16–430 and generates a premature stop. The F0 founder was backcrossed two times to wild-type mice and the F2 generation was used to generate Csf1em1(CSF1)Bdes;Rag2em1Bdes double-mutant mice (short name: hCsf1Bdes).
References
  • A versatile mouse model to advance human microglia transplantation research in neurodegenerative diseases.;Serneels Lutgarde, Sierksma Annerieke, Pasciuto Emanuela, Geric Ivana, Nair Arya, Martinez-Muriana Anna, Snellinx An, De Strooper Bart, ;2025;Molecular neurodegeneration;20;29; 40069774
Homozygous fertileyes
Homozygous viableyes
Homozygous matings requiredyes
Immunocompromisedyes

Information from EMMA

Archiving centreInstitute of Molecular Genetics, Prague, Czech Republic

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

MGI phenotypes (gene matching)
  • fragile skeleton / MGI
  • abnormal bone marrow cavity morphology / MGI
  • osteoporosis / MGI
  • osteopetrosis / MGI
  • abnormal parietal bone morphology / MGI
  • failure of tooth eruption / MGI
  • absent incisors / MGI
  • abnormal trabecular bone morphology / MGI
  • decreased compact bone thickness / MGI
  • abnormal microglial cell morphology / MGI
  • abnormal long bone hypertrophic chondrocyte zone / MGI
  • decreased circulating phosphate level / MGI
  • decreased leukocyte cell number / MGI
  • decreased monocyte cell number / MGI
  • extramedullary hematopoiesis / MGI
  • increased granulocyte number / MGI
  • decreased bone marrow cell number / MGI
  • domed cranium / MGI
  • short limbs / MGI
  • abnormal tibia morphology / MGI
  • abnormal femur morphology / MGI
  • abnormal autopod morphology / MGI
  • short tail / MGI
  • abnormal mammary gland development / MGI
  • abnormal branching of the mammary ductal tree / MGI
  • small spleen / MGI
  • thymus cortex hypoplasia / MGI
  • abnormal ovary morphology / MGI
  • abnormal ovarian folliculogenesis / MGI
  • decreased body weight / MGI
  • abnormal mating frequency / MGI
  • reduced male mating frequency / MGI
  • abnormal eating behavior / MGI
  • abnormal circulating calcium level / MGI
  • impaired embryo implantation / MGI
  • abnormal postnatal growth / MGI
  • postnatal growth retardation / MGI
  • abnormal lactation / MGI
  • reduced fertility / MGI
  • reduced male fertility / MGI
  • reduced female fertility / MGI
  • abnormal ovulation / MGI
  • decreased litter size / MGI
  • premature death / MGI
  • abnormal spleen red pulp morphology / MGI
  • abnormal bone marrow morphology / MGI
  • abnormal bone marrow cell morphology/development / MGI
  • abnormal sperm number / MGI
  • decreased corpora lutea number / MGI
  • decreased mature ovarian follicle number / MGI
  • oligozoospermia / MGI
  • decreased circulating testosterone level / MGI
  • abnormal bone remodeling / MGI
  • no phenotypic analysis / MGI
  • amyloid beta deposits / MGI
  • decreased ovulation rate / MGI
  • impaired granulosa cell differentiation / MGI
  • increased width of hypertrophic chondrocyte zone / MGI
  • abnormal uterus development / MGI
  • abnormal bone structure / MGI
  • abnormal compact bone morphology / MGI
  • impaired macrophage chemotaxis / MGI
  • decreased macrophage cell number / MGI
  • abnormal masseter muscle morphology / MGI
  • decreased length of long bones / MGI
  • abnormal thyroid parafollicular C-cell morphology / MGI
  • abnormal auditory brainstem response / MGI
  • abnormal vestibular system physiology / MGI
  • abnormal hematopoietic stem cell morphology / MGI
  • increased testis weight / MGI
  • abnormal testis physiology / MGI
  • decreased spleen weight / MGI
  • abnormal osteoclast morphology / MGI
  • abnormal osteoclast cell number / MGI
  • decreased osteoclast cell number / MGI
  • abnormal osteoblast morphology / MGI
  • decreased bone resorption / MGI
  • abnormal osteoblast physiology / MGI
  • increased T cell number / MGI
  • decreased lymphocyte cell number / MGI
  • decreased B cell number / MGI
  • decreased susceptibility to atherosclerosis / MGI
  • abnormal Langerhans cell physiology / MGI
  • behavior/neurological phenotype / MGI
  • osteosclerosis / MGI
  • abnormal skeleton morphology / MGI
  • increased bone mass / MGI
  • abnormal mammary gland growth during pregnancy / MGI
  • abnormal mammary gland growth during lactation / MGI
  • increased long bone epiphyseal plate size / MGI
  • abnormal Kupffer cell morphology / MGI
  • abnormal Langerhans cell morphology / MGI
  • absent Langerhans cell / MGI
  • abnormal perivascular macrophage morphology / MGI
  • abnormal myeloid leukocyte morphology / MGI
  • abnormal osteoclast differentiation / MGI
  • abnormal neurite morphology / MGI
  • slow postnatal weight gain / MGI
  • abnormal osteocyte morphology / MGI
  • abnormal splenic cell ratio / MGI
  • abnormal ovarian follicle number / MGI
  • decreased physiological sensitivity to xenobiotic / MGI
  • prolonged estrous cycle / MGI
  • abnormal proestrus / MGI
  • myometrium hypoplasia / MGI
  • endometrium hypoplasia / MGI
  • necrospermia / MGI
  • abnormal splenocyte physiology / MGI
  • decreased trabecular bone thickness / MGI
  • abnormal mammary gland lobule morphology / MGI
  • abnormal mammary gland alveolus morphology / MGI
  • decreased fertilization frequency / MGI
  • decreased hippocampus pyramidal cell number / MGI
  • abnormal visual evoked potential / MGI
  • increased bone trabecula number / MGI
  • increased trabecular bone mass / MGI
  • increased trabecular bone volume / MGI
  • postnatal lethality, incomplete penetrance / MGI
  • decreased secondary ovarian follicle number / MGI
  • abnormal tooth root development / MGI
  • impaired osteoblast differentiation / MGI
  • abnormal auditory brainstem response waveform shape / MGI
  • thymus medulla atrophy / MGI
  • decreased bone mineralization / MGI
  • round snout / MGI
  • abnormal dentin mineralization / MGI
  • increased osteocyte apoptosis / MGI
  • abnormal osteocyte lacuna morphology / MGI
  • abnormal osteocyte dendritic process morphology / MGI
  • abnormal dental follicle morphology / MGI
  • abnormal predentin morphology / MGI
  • absent teeth / MGI
  • decreased monocyte cell number / MGI
  • increased granulocyte number / MGI
  • decreased bone marrow cell number / MGI
  • alopecia / MGI
  • abnormal digestive system morphology / MGI
  • abnormal intestinal epithelium morphology / MGI
  • abnormal intestinal mucosa morphology / MGI
  • abnormal spleen morphology / MGI
  • small spleen / MGI
  • spleen hypoplasia / MGI
  • abnormal Peyer's patch morphology / MGI
  • abnormal thymus morphology / MGI
  • decreased thymocyte number / MGI
  • abnormal immune system cell morphology / MGI
  • decreased body size / MGI
  • abnormal humoral immune response / MGI
  • arrested B cell differentiation / MGI
  • decreased IgG level / MGI
  • decreased IgM level / MGI
  • decreased IgA level / MGI
  • thymus hypoplasia / MGI
  • arrested T cell differentiation / MGI
  • lung inflammation / MGI
  • neoplasm / MGI
  • abnormal B cell differentiation / MGI
  • no abnormal phenotype detected / MGI
  • small lymph nodes / MGI
  • abnormal lymph node morphology / MGI
  • abnormal lymphopoiesis / MGI
  • abnormal pre-B cell morphology / MGI
  • increased susceptibility to infection / MGI
  • abnormal double-negative T cell morphology / MGI
  • abnormal double-positive T cell morphology / MGI
  • increased susceptibility to bacterial infection / MGI
  • abnormal effector T cell morphology / MGI
  • abnormal macrophage physiology / MGI
  • abnormal B cell number / MGI
  • abnormal B cell physiology / MGI
  • abnormal immune system organ morphology / MGI
  • colitis / MGI
  • absent Peyer's patches / MGI
  • increased natural killer cell mediated cytotoxicity / MGI
  • erythroderma / MGI
  • abnormal lymphocyte physiology / MGI
  • abnormal B cell morphology / MGI
  • decreased lymphocyte cell number / MGI
  • decreased B cell number / MGI
  • decreased T cell number / MGI
  • decreased susceptibility to parasitic infection / MGI
  • decreased double-negative T cell number / MGI
  • increased double-negative T cell number / MGI
  • decreased double-positive T cell number / MGI
  • decreased T cell proliferation / MGI
  • cachexia / MGI
  • increased macrophage cell number / MGI
  • abnormal T-helper 1 physiology / MGI
  • decreased susceptibility to type IV hypersensitivity reaction / MGI
  • abnormal response to transplant / MGI
  • abnormal T cell morphology / MGI
  • decreased NK T cell number / MGI
  • decreased CD4-positive, alpha beta T cell number / MGI
  • decreased CD8-positive, alpha-beta T cell number / MGI
  • lymph node hypoplasia / MGI
  • decreased pre-B cell number / MGI
  • decreased mature B cell number / MGI
  • absent mature B cells / MGI
  • increased immature B cell number / MGI
  • decreased immature B cell number / MGI
  • abnormal gamma-delta T cell differentiation / MGI
  • decreased spleen white pulp amount / MGI
  • abnormal interferon secretion / MGI
  • abnormal chemokine secretion / MGI
  • abnormal T cell receptor V(D)J recombination / MGI
  • abnormal immunoglobulin V(D)J recombination / MGI
  • absent Hassall's corpuscle / MGI
  • small inguinal lymph nodes / MGI
  • decreased susceptibility to bacterial infection induced morbidity/mortality / MGI
  • increased DN3 thymocyte number / MGI
  • abnormal stomach mucosa morphology / MGI
  • small cervical lymph nodes / MGI

Literature references

  • A versatile mouse model to advance human microglia transplantation research in neurodegenerative diseases.;Serneels Lutgarde, Sierksma Annerieke, Pasciuto Emanuela, Geric Ivana, Nair Arya, Martinez-Muriana Anna, Snellinx An, De Strooper Bart, ;2025;Molecular neurodegeneration;20;29; 40069774

Information on how we integrate external resources can be found here

Register interest

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), as well as a CRISPR surcharge.

More details on pricing and delivery times

Practical information

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.

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Legally binding conditions for the transfer

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