Overview

This strain has been discontinued.

Please consider a related strain (Stock No. 001815). Alternatively, please search the JAX Mice database for other strains which may be suitable for your studies or contact Technical Support for assistance.

Donating Investigator

Daniel J. McBride, University of Maryland, Schl of Medicine

Genetic overview

Genetic Background	Generation

Col1a2^tm1.1Mcbr

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence)	Col1a2	collagen, type I, alpha 2

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Research Applications

Developmental Biology Research
Cell Biology Research

View All Research Applications

Details

Detailed Description

These mice harbor a point mutation knock-in patterned after the variant found among Old Order Amish kindred (OOA) of Lancaster County, Pennsylvania. Mice exhibit reduced body mass and reduced bone mass density by 2 months of age. Homozygotes do not survive to weaning age. These mutant mice express mutant type I collagen similar to that observed in humans with osteogenesis imperfecta. Incorporation of the point mutation was verified by sequence analysis. Mutant mRNA is detected by RT-PCR analysis of total RNA.

Development

A targeting vector containing a loxP flanked neomycin resistance cassette was used to introduce a point mutation equivalent to the human G610C mutation, into exon 33 (Note: mouse exon 33 is equivalent to human exon 35). The construct was electroporated into 129/SvEv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J. Male animals were then crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J female mice (Stock No. 003724) to remove the selection cassette. The mice were backcrossed to C57BL/6J for 4 generations before arriving at The Jackson Laboratory. Upon arrival the mice were backcrossed to C57BL/6J for 1 generation.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

McBride DJ. 2007. A knock-in mutation of Col1a2 MGI Direct Data SubmissionMGI: J:121691

View All References

Genetics

Col1a2^tm1.1Mcbr

Allele Symbol: Col1a2^tm1.1Mcbr

Allele Name	targeted mutation 1.1, Daniel J McBride
Allele Type	Targeted (Inserted expressed sequence)
Allele Synonym(s)	G610C Neo-; G610C OI (Amish)
Gene Symbol and Name	Col1a2, collagen, type I, alpha 2
Gene Synonym(s)
Promoter	Col1a2, collagen, type I, alpha 2, mouse, laboratory
Strain of Origin	129/SvEv
Chromosome	6
Molecular Note	A floxed neo cassette was inserted upstream of exon 35 and a G to T mutation was inserted in exon 35 resulting in a glycine to cysteine mutation at codon 706. Cre mediated recombination removed the neo cassette.
Mutations Made By	Daniel McBride, University of Maryland, Schl of Medicine

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

osteogenesis imperfecta

Research Areas By Phenotype

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

Developmental Biology Research
- Skeletal Defects
- Defects in Extracellular Matrix Molecules
Cell Biology Research
- Defects in Extracellular Matrix 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: Col1a2^tm1.1Mcbr/Col1a2⁺
(C3H/HeJ x B6.129-Col1a2)F1

growth/size/body region phenotype

decreased body weight

skeleton phenotype

decreased bone trabecula number
- fewer and more widely spaced trabeculae

decreased bone volume

decreased compact bone thickness

increased volumetric bone mineral density
- cortical volumetric tissue mineral density (vTMD) is elevated in the femur

decreased bone mineral content
- lower cortical volumetric tissue mineral content
- decreased bone mineral content

increased bone mineral density
- Background Sensitivity - bone mineral density is lowest on the mixed C3H/HeJ and C57BL/6 background compared to F1 crosses to A/J, BALB/cByJ, or FVB/NJ

decreased bone strength
- femurs are weaker and more brittle

decreased compact bone area

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(FVB/NJ x B6.129-Col1a2)F1

growth/size/body region phenotype

decreased body weight

skeleton phenotype

increased bone mineral density
- Background Sensitivity - bone mineral density is higher on the mixed FVB/NJ and C57BL/6 background compared to F1 crosses to C3H/HeJ but lower compared to F1 crosses to A/J or BALB/cByJ

decreased bone mineral content

decreased bone strength
- femurs are weaker and more brittle

increased volumetric bone mineral density
- cortical volumetric tissue mineral density (vTMD) is elevated in the femur

decreased bone trabecula number
- fewer and more widely spaced trabeculae

decreased bone volume

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(A/J x B6.129-Col1a2)F1

growth/size/body region phenotype

decreased body weight

skeleton phenotype

decreased compact bone area

decreased bone mineral content
- decreased bone mineral content
- lower cortical volumetric tissue mineral content

decreased bone strength
- femurs are weaker and more brittle

decreased bone trabecula number
- fewer and more widely spaced trabeculae

decreased bone volume

decreased compact bone thickness

increased volumetric bone mineral density
- cortical volumetric tissue mineral density (vTMD) is elevated in the femur

increased bone mineral density
- Background Sensitivity - bone mineral density is highest on the mixed A/J and C57BL/6 background compared to F1 crosses to BALB/cByJ, FVB/NJ, or C3H/HeJ

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(BALB/cByJ x B6.129-Col1a2)F1

growth/size/body region phenotype

decreased body weight

skeleton phenotype

increased bone mineral density
- Background Sensitivity - bone mineral density is higher on the mixed BALB/cByJ and C57BL/6 background compared to F1 crosses to FVB/NJ, or C3H/HeJ but lower compared to F1 crosses to A/J

decreased bone strength
- femurs are weaker and more brittle

decreased bone trabecula number
- fewer and more widely spaced trabeculae

decreased bone volume

increased volumetric bone mineral density
- cortical volumetric tissue mineral density (vTMD) is elevated in the femur

decreased compact bone area

decreased compact bone thickness

decreased bone mineral content
- lower cortical volumetric tissue mineral content
- decreased bone mineral content

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

Genotype: Col1a2^tm1.1Mcbr/Col1a2^tm1.1Mcbr
B6.129(Cg)-Col1a2

mortality/aging

perinatal lethality, complete penetrance
- no homozygous mice are recovered but dead pups are found within 24 hours of birth

preweaning lethality, complete penetrance
- homozygous mice do not survive to weaning age

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
B6.129(Cg)-Col1a2

growth/size/body region phenotype

decreased body weight
- mice show reduced body mass compared to wild-type

References

McBride DJ. 2007. A knock-in mutation of Col1a2 MGI Direct Data SubmissionMGI: J:121691

Additional - Col1a2^tm1.1Mcbr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Col1a2
- End Point Analysis:Col1a2-EP
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes do not survive to weaning. The donating investigator uses a breeding scheme of heterozygote x wildtype. Please note: heterozygous mice exhibit reduced body mass and reduced bone mass density by 2 months of age.
- Additional Breeding and Husbandry Support

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

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Col1a2tm1.1Mcbr

Allele Symbol: Col1a2tm1.1Mcbr

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Col1a2tm1.1Mcbr/Col1a2+(C3H/HeJ x B6.129-Col1a2)F1

growth/size/body region phenotype

skeleton phenotype

Genotype: Col1a2tm1.1Mcbr/Col1a2+(FVB/NJ x B6.129-Col1a2)F1

growth/size/body region phenotype

skeleton phenotype

Genotype: Col1a2tm1.1Mcbr/Col1a2+(A/J x B6.129-Col1a2)F1

growth/size/body region phenotype

skeleton phenotype

Genotype: Col1a2tm1.1Mcbr/Col1a2+(BALB/cByJ x B6.129-Col1a2)F1

growth/size/body region phenotype

skeleton phenotype

Genotype: Col1a2tm1.1Mcbr/Col1a2tm1.1McbrB6.129(Cg)-Col1a2

mortality/aging

Genotype: Col1a2tm1.1Mcbr/Col1a2+B6.129(Cg)-Col1a2

growth/size/body region phenotype

References

Additional - Col1a2tm1.1Mcbr related

Genotyping Protocols

Breeding Considerations

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Col1a2^tm1.1Mcbr

Allele Symbol: Col1a2^tm1.1Mcbr

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(C3H/HeJ x B6.129-Col1a2)F1

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(FVB/NJ x B6.129-Col1a2)F1

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(A/J x B6.129-Col1a2)F1

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
(BALB/cByJ x B6.129-Col1a2)F1

Genotype: Col1a2^tm1.1Mcbr/Col1a2^tm1.1Mcbr
B6.129(Cg)-Col1a2

Genotype: Col1a2^tm1.1Mcbr/Col1a2⁺
B6.129(Cg)-Col1a2

Additional - Col1a2^tm1.1Mcbr related