Overview

Also Known As:CD18^-

Homozygous mutant mice show an increased neutrophil count, and a decreased inflammatory response to peritonitis. Responses to delayed-type hypersensitivity and rejection of transplanted tissue are impaired. This strain serves as a model for the moderate form of human CD18 deficiency.

Donating Investigator

Dr. Arthur Beaudet, Baylor College of Medicine

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Itgb2^tm1Bay

Allele Type	Gene Symbol	Gene Name
Targeted (Hypomorph)	Itgb2	integrin beta 2

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Research Applications

Dermatology Research
Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
Mouse/Human Gene Homologs
Cell Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Itgb2^tm1Bay mutation are viable and fertile. Homozygous mutant mice show an increased neutrophil count, and a decreased inflammatory response to peritonitis. Responses to delayed-type hypersensitivity and rejection of transplanted tissue are impaired. PLEASE NOTE: The Itgb2^tm1Bay allele is not a null mutation; it is a hypomorphic mutation which results in the expression of very low levels of Itgb2 protein. This strain serves as a model for the moderate form of human CD18 deficiency.

Development

The Itgb2^tm1Bay mutant strain was developed in the laboratory of Dr. Arthur Beaudet at Baylor College of Medicine. The 129-derived AB1 ES cell line was used. The C57BL/6J strain was produced by backcrossing the Itgb2^tm1Bay mutation 10 times to C57BL/6J inbred mice.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wilson RW; Ballantyne CM; Smith CW; Montgomery C; Bradley A; O'Brien WE; Beaudet AL. 1993. Gene targeting yields a CD18-mutant mouse for study of inflammation. J Immunol 151(3):1571-8PubMed: 8101543 MGI: J:13599

View All References

Genetics

Itgb2^tm1Bay

Allele Symbol: Itgb2^tm1Bay

Allele Name	targeted mutation 1, Baylor College of Medicine
Allele Type	Targeted (Hypomorph)
Allele Synonym(s)	CD18^-; CD18^hypo; CD18^low; Itgb2^hypo
Gene Symbol and Name	Itgb2, integrin beta 2
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	10
Molecular Note	An insertion mutation that duplicates exons 2 and 3 with interruption of one copy of exon 3 with a neomycin cassette. This is not a null mutation but rather a hypomorph expressing very low levels of ITGB2 protein.
Mutations Made By	Dr. Arthur Beaudet, Baylor College of Medicine

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

leukocyte adhesion deficiency 1

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

psoriasis

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Itgb2^tm1Bay related

Dermatology Research
- Skin and Hair Texture Defects
Developmental Biology Research
- Defects in Extracellular Matrix Molecules
- Defects in Cell Adhesion Molecules
Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Inflammation
Mouse/Human Gene Homologs
- leukocyte adhesion deficiency, type I
Cell Biology Research
- Defects in Cell Adhesion Molecules

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd * PL/J

homeostasis/metabolism phenotype

abnormal cytokine level
- increase in Th1 cytokines, IFN-gamma, IL-2, and IL-10, in T cells from skin lesion-draining lymph nodes

immune system phenotype

abnormal cytokine level
- increase in Th1 cytokines, IFN-gamma, IL-2, and IL-10, in T cells from skin lesion-draining lymph nodes

enlarged lymph nodes
- displayed reactive lymphadenopathy

increased lymphocyte cell number

increased neutrophil cell number

increased T-helper 1 cell number
- increase in Th1-type cytokine-producing CD4+ T cells but not in Th2-type cytokine producing T cells

myeloid hyperplasia
- exhibited myeloid hyperplasia in the bone marrow

abnormal T cell activation
- mice show increased state of activation in CD4+ T cells

increased leukocyte cell number
- Background Sensitivity - numbers of white blood cells were increased to a higher extent than on a 129S7/SvEvBrd background

increased T cell number
- number of CD4+ and CD8+ T cells is highly increased in the epidermis and dermis

dermatitis
- depletion of CD4+ T cells, but not of CD8+ T cells, with depleting antibodies results in resolution of the psoriasiform dermatitis after 6 weeks of treatment
- mice develop psoriasiform dermatitis
- developed a progressive dermatitis, characterized by erythema, alopecia, and scale and crust formation

abnormal spleen morphology
- exhibited myeloid hyperplasia in the spleen

increased interferon-gamma secretion
- CD90+ T cells release up to 40-fold higher concentrations of IFN-gamma when cultured with anti-CD3 and anti-CD28 antibodies

increased eosinophil cell number

increased basophil cell number

increased monocyte cell number

integument phenotype

abnormal skin condition

alopecia
- progressively developed in the facial region and/or base of the tail

mixed cellular infiltration to dermis
- progressive dermatitis with a dermal infiltrate consisting of granulocytes, lymphocytes, histiocytes and scattered mast cells

orthokeratosis
- skin exhibited orthohyperkeratosis

psoriasis
- had irregular psoriasiform hyperplasia of the epidermis and subcorneal microabscesses
- mice develop psoriasiform dermatitis

scaly skin
- severely affected mice developed scales and crusts in the dorsum of the trunk, the abdomen, and the neck

epidermal hyperplasia
- irregular psoriasiform hyperplasia of the epidermis

reddish skin
- dermatitis was characterized by erythema

abnormal hair follicle dermal papilla morphology
- vessels within the dermal papillae were dilated

dermatitis
- mice develop psoriasiform dermatitis
- developed a progressive dermatitis, characterized by erythema, alopecia, and scale and crust formation
- depletion of CD4+ T cells, but not of CD8+ T cells, with depleting antibodies results in resolution of the psoriasiform dermatitis after 6 weeks of treatment

abnormal dermal layer morphology
- dermal collagen appeared disorganized

abnormal epidermal layer morphology
- occasionally developed focal spongiosis and erosion of the epidermis

parakeratosis

hematopoietic system phenotype

increased eosinophil cell number

increased T cell number
- number of CD4+ and CD8+ T cells is highly increased in the epidermis and dermis

increased neutrophil cell number

increased T-helper 1 cell number
- increase in Th1-type cytokine-producing CD4+ T cells but not in Th2-type cytokine producing T cells

increased lymphocyte cell number

myeloid hyperplasia
- exhibited myeloid hyperplasia in the bone marrow

thrombocytosis

increased basophil cell number

increased monocyte cell number

abnormal spleen morphology
- exhibited myeloid hyperplasia in the spleen

abnormal T cell activation
- mice show increased state of activation in CD4+ T cells

increased leukocyte cell number
- Background Sensitivity - numbers of white blood cells were increased to a higher extent than on a 129S7/SvEvBrd background

mammalian phenotype

integument phenotype
- Background Sensitivity - associated phenotypes appear on the PL/J background but not on a C57BL/6 or 129S7/SvEvBrd background

pigmentation phenotype
- Background Sensitivity - associated phenotype appears on the PL/J background but not on a C57BL/6 or 129S7/SvEvBrd background

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6J

hematopoietic system phenotype

myeloid hyperplasia
- myeloid hyperplasia in bone marrow

abnormal spleen red pulp morphology
- myeloid hyperplasia of splenic red pulp

immune system phenotype

myeloid hyperplasia
- myeloid hyperplasia in bone marrow

abnormal spleen red pulp morphology
- myeloid hyperplasia of splenic red pulp

mammalian phenotype

integument phenotype
- Background Sensitivity - did not develop progressive dermatitis in the C57BL/6J background

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd

mammalian phenotype

integument phenotype
- Background Sensitivity - did not develop progressive dermatitis in the 129S7/SvEvBrd background

hematopoietic system phenotype

increased leukocyte cell number
- Background Sensitivity - increased total leukocyte counts however less elevated than on the PL/J background

increased granulocyte number

increased lymphocyte cell number

immune system phenotype

decreased inflammatory response
- decreased inflammatory response to i.p. injection of thioglycollate showing decreased migration of neutrophils into the peritoneal cavity
- delayed rejection of cardiac transplants

increased leukocyte cell number
- Background Sensitivity - increased total leukocyte counts however less elevated than on the PL/J background

increased lymphocyte cell number

increased granulocyte number

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6J * PL/J

immune system phenotype

dermatitis
- Background Sensitivity - 23.5% of the F2 progeny from a PL/J x C57BL/6J intercross develop psoriasiform dermatitis, which is not observed on a 129S7/SvEvBrd or a mixed 129S7/SvEvBrd and C57BL/6J background

integument phenotype

dermatitis
- Background Sensitivity - 23.5% of the F2 progeny from a PL/J x C57BL/6J intercross develop psoriasiform dermatitis, which is not observed on a 129S7/SvEvBrd or a mixed 129S7/SvEvBrd and C57BL/6J background

alopecia
- approximately half of affected F2 mice develop severe disease with various degrees of alopecia

psoriasis
- 23.5% of the F2 progeny from a PL/J x C57BL/6J intercross develop chronic inflammatory skin disease with highly variable severity

reddish skin
- Background Sensitivity - approximately half of affected F2 mice develop only mild disease with erythema and/or dry skin, which is not observed on a 129S7/SvEvBrd or a mixed 129S7/SvEvBrd and C57BL/6J background

mammalian phenotype

integument phenotype
- Background Sensitivity - F1 mice from intercrosses of homozygotes on PL/J and C57BL/6J backgrounds did not develop progressive dermatitis, however when F1 mice were backcrossed to homozygotes on the PL/J background, 50% developed dermatitis

The following phenotype relates to a compound genotype created using this strain

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
B6.129S7-Itgb2/J

cardiovascular system phenotype

decreased susceptibility to induced choroidal neovascularization
- at 2 weeks after laser injury, volume of choroidal neovascularization (CNV) is reducedby ~67.0% compared to wild-type mice
- mutants have markedly smaller CNV membranes 2 weeks after injury compared to wild-type

abnormal retinal vasculature morphology
- in diabetes models, mutants exhibit decreased retinal-blood barrier breakdown compared to diabetic controls at 11 months

homeostasis/metabolism phenotype

increased circulating glucose level
- blood glucose levels are significantly increased in mutants and controls with streptozotocin treatment or high galactose diet

mortality/aging

premature death
- mutants and wild-type mice treated with streptozotocin to induce diabetes display significantly increased mortality after 12 months of disease compared to untreated controls

vision/eye phenotype

abnormal eye physiology
- in the diabetes models, 11-month diabetic mutants have decreased numbers of injured endothelial cells (<5%) compared to diabetic wild-type controls

abnormal retina morphology
- at 11 months, numbers of normal appearing pericytes in retinas of diabetic mutants are significantly greater than number in diabetic wild-type controls
- compared to diabetic wild-type controls, number of endothelial cells in diabetic mutants are higher and comparable to non-diabetic wild-type controls
- 11-month diabetic wild-type mice have 3.8-fold more acellular capillaries compared to non-diabetic controls; in diabetic mutants, this pathology is suppressed by 60% with number of acellular capillaries similar to that in non-diabetic wild-type controls
- m number in non-diabetic controls
- following laser photocoagulation (1,2, and 4 weeks after), significantly less pathologically significant leakage (fewer grade-2B lesions) develops in mutants compared to wild-type
- no basement membrane thickening is observed in diabetic and galactosemic mutants compared to that observed in diabetic and galactosemic wild-type controls
- diabetic wild-type mice at 11 months of disease have a 3.1-fold increase in adherent leukocyte number compared with non-diabetic controls
- in the galactose- and streptozotocin-induced diabetes models, after 11 months, mutants have fewer adherent leukocytes in the retina compared to diabetic controls; number of adherent leukocytes in the retina in 11-month diabetic mutants does not differ from number in non-diabetic controls
- at 22 months, galactosemic mutants show almost no endothelial cell loss, no pericyte loss, and less acellular capillary formation (by 60%) than galactosemic wild-type controls compared to euglycemic wild-type mice
- less mice have 3 or more grade-2B lesions in each eye compared with wild-type

decreased susceptibility to induced choroidal neovascularization
- at 2 weeks after laser injury, volume of choroidal neovascularization (CNV) is reducedby ~67.0% compared to wild-type mice
- mutants have markedly smaller CNV membranes 2 weeks after injury compared to wild-type

abnormal retinal vasculature morphology
- in diabetes models, mutants exhibit decreased retinal-blood barrier breakdown compared to diabetic controls at 11 months

References

Wilson RW; Ballantyne CM; Smith CW; Montgomery C; Bradley A; O'Brien WE; Beaudet AL. 1993. Gene targeting yields a CD18-mutant mouse for study of inflammation. J Immunol 151(3):1571-8PubMed: 8101543 MGI: J:13599

Additional References

Bullard DC; Scharffetter-Kochanek K; McArthur MJ; Chosay JG; McBride ME; Montgomery CA; Beaudet AL. 1996. A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice. Proc Natl Acad Sci U S A 93(5):2116-21PubMed: 8700894 MGI: J:32126
Kadono T; Venturi GM; Steeber DA; Tedder TF. 2002. Leukocyte rolling velocities and migration are optimized by cooperative L-selectin and intercellular adhesion molecule-1 functions. J Immunol 169(8):4542-50PubMed: 12370391 MGI: J:79530
Papayannopoulou T; Priestley GV; Nakamoto B; Zafiropoulos V; Scott LM; Harlan JM. 2001. Synergistic mobilization of hemopoietic progenitor cells using concurrent beta1 and beta2 integrin blockade or beta2-deficient mice. Blood 97(5):1282-8PubMed: 11222371 MGI: J:67767
Wu HS; Kolonoski P; Chang YY; Bermudez LE. 2000. Invasion of the brain and chronic central nervous system infection after systemic Mycobacterium avium complex infection in mice. Infect Immun 68(5):2979-84PubMed: 10768998 MGI: J:61694

Additional - Itgb2^tm1Bay related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Itgb2
- QPCR:Itgb2QPCR2
- Genotyping resources and troubleshooting
Breeding Considerations

The Itgb2^tm1Bay strain is maintained by homozygous sibling matings. Homozygous mice may be ordered. Expected coat color from breeding:Black
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the CD18^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002128 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Homozygous for Itgb2<tm1Bay>, 1 pair minimum

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:CD18-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Itgb2tm1Bay

Allele Symbol: Itgb2tm1Bay

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Itgb2tm1Bay related

Mammalian Phenotype Terms by Genotype

Genotype: Itgb2tm1Bay/Itgb2tm1Bayinvolves: 129S7/SvEvBrd * PL/J

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

hematopoietic system phenotype

mammalian phenotype

Genotype: Itgb2tm1Bay/Itgb2tm1Bayinvolves: 129S7/SvEvBrd * C57BL/6J

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Itgb2tm1Bay/Itgb2tm1Bayinvolves: 129S7/SvEvBrd

mammalian phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Itgb2tm1Bay/Itgb2tm1Bayinvolves: 129S7/SvEvBrd * C57BL/6J * PL/J

immune system phenotype

integument phenotype

mammalian phenotype

Genotype: Itgb2tm1Bay/Itgb2tm1BayB6.129S7-Itgb2/J

cardiovascular system phenotype

homeostasis/metabolism phenotype

mortality/aging

vision/eye phenotype

References

Additional References

Additional - Itgb2tm1Bay related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:CD18^-

Itgb2^tm1Bay

Allele Symbol: Itgb2^tm1Bay

Genotype: Itgb2^tm1Bay related

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd * PL/J

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6J

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6J * PL/J

Genotype: Itgb2^tm1Bay/Itgb2^tm1Bay
B6.129S7-Itgb2/J

Additional - Itgb2^tm1Bay related