Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Rudolf Jaenisch,   Massachusetts Institute of Technology

Appearance
white-bellied agouti
Related Genotype: A^w/A^w

Description
Homozygous mice are viable and develop to young adulthood without obvious differences from wildtype mice. As the mice age they develop fibrosis in the dermis characterized by a thickening and roughening of the skin, which is similar to that seen in human scleroderma. Homozygous females develop postpartum abnormalities of the uterus caused by a failure of collagen resorption. They have slightly reduced litter sizes and significantly fewer litters than normal wildtype mice. A secondary collagenase cleavage site was found in the mutant protein that could be cleaved by rat collagenase but not by human collagenase.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Col1a1

006911	B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm2(tetO-Pou5f1)Jae/J
002197	C57BL/6-Col1a1Mov13/J

View Strains carrying other alleles of Col1a1     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Col1a1^tm1Jae/Col1a1⁺

        either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)

• reproductive system phenotype
• abnormal uterus morphology (MGI Ref ID J:26504)
  • collagen accumulation in the uteri of heterozygous mutants was less pronounced relative to homozygous mutants
• decreased litter size (MGI Ref ID J:26504)
  • heterozygous females had slightly reduced litter sizes and significantly fewer litters than wild-type females
• skin/coat/nails phenotype
• partial hair loss (MGI Ref ID J:26504)
  • heterozygotes developed patchy hair loss
• thick dermal layer (MGI Ref ID J:26504)
  • at ~7 months, heterozygotes developed dermal fibrosis, similar to scleroderma, and skin ulcerations
  • mutant skin displayed a significant increase in collagen extending through to the deep dermis
  • heterozygous males and females developed similar but milder skin abnormalities relative to age-matched homozygous males

Col1a1^tm1Jae/Col1a1^tm1Jae

        either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)

• reproductive system phenotype
• abnormal uterus morphology (MGI Ref ID J:26504)
  • homozygous females developed postpartum abnormalities of the uterus - including persistence of nodules containing type I collagen in the uterine wall - caused by a failure of collagen resorption
  • occasionally, virgin homozygous females showed small accumulations of collagen in the myometrium of the uterus
• decreased litter size (MGI Ref ID J:26504)
  • mutant females had slightly reduced litter sizes and significantly fewer litters than wild-type females
• skin/coat/nails phenotype
• partial hair loss (MGI Ref ID J:26504)
  • homozygotes developed patchy hair loss
• thick dermal layer (MGI Ref ID J:26504)
  • homozygotes were viable, resistant to collagenase action, and developed normally to young adulthood
  • at ~7 months, homozygotes developed dermal fibrosis, similar to scleroderma, and skin ulcerations
  • mutant skin displayed a significant increase in collagen extending through to the deep dermis
  • homozygous females developed similar but milder skin abnormalities relative to age-matched homozygous males

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Col1a1^tm1Jae/Col1a1^tm1Jae

        involves: 129S4/SvJae * C57BL/6

• craniofacial phenotype
• abnormal calvaria morphology (MGI Ref ID J:90884)
  • at >4 weeks of age, mutants showed increased bone deposition in calvariae mainly at the inner periosteal surface adjacent to the dura mater
  • calvarial thickness nearly doubled by ~10 months of age
  • homozygotes had normal circulating levels of PTH, but showed increased calcein labeling of calvarial surfaces
• growth/size phenotype
• decreased body weight (MGI Ref ID J:82606)
  • homozygotes showed a normal mean body weight throughout the 36-wk observation period, except for a 9.8% reduction at 18 wks
• limbs/digits/tail phenotype
• abnormal skeleton extremities morphology (MGI Ref ID J:53079)
  • adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone
• skeleton phenotype
• *normal* skeleton phenotype (MGI Ref ID J:85591)
  • homozygotes showed normal tooth eruption
• abnormal calvaria morphology (MGI Ref ID J:90884)
  • at >4 weeks of age, mutants showed increased bone deposition in calvariae mainly at the inner periosteal surface adjacent to the dura mater
  • calvarial thickness nearly doubled by ~10 months of age
  • homozygotes had normal circulating levels of PTH, but showed increased calcein labeling of calvarial surfaces
• abnormal joint morphology (MGI Ref ID J:53079)
  • adult homozygotes developed joint contractures
• abnormal osteoblast formation (MGI Ref ID J:85591)
  • at 4 weeks, homozygotes showed an increase in tibial trabecular bone volume despite an overall decrease in osteoblast activity in trabecular bone
  • in contrast, homozygotes displayed normal tibial cortical bone thickness, and a relatively normal tibial periosteal mineral apposition rate
  • at greater 4 weeks of age, mutants began to show increased bone deposition of endosteal trabecular bone in tibial/femoral bones
• abnormal osteoblast morphology (MGI Ref ID J:90884)
  • beginning at about 2 weeks of age, homozygotes showed increased osteoblast and osteocyte apoptosis, despite increased bone deposition
• abnormal osteocyte morphology (MGI Ref ID J:90884)
  • beginning at about 2 weeks of age, homozygotes showed increased osteoblast and osteocyte apoptosis, despite increased bone deposition
  • at greater than 2 weeks of age, homozygotes showed loss of osteocytes from their lacunae in the calvariae and in the shafts of long bones
  • the number of "empty" lacunae increased with age
• abnormal osteoclast physiology (MGI Ref ID J:53079)
  • in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts
  • the bone resorption area and the number of osteoclasts/mm2 were significantly increased (~5-fold) after PTH injection in wild-type, but not in homozygous mutant mice
  • homozygotes were not resistant to other skeletal effects of PTH
  • after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type
• abnormal skeleton extremities morphology (MGI Ref ID J:53079)
  • adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone
• failure of secondary bone resorption (MGI Ref ID J:85591)
  • homozygotes showed impaired osteoclastic bone resorption in trabecular bone: namely, an increase in osteoclast number and surface in long bones
• osteopetrosis (MGI Ref ID J:85591)
  • homozygotes exhibited a mild osteopetrotic phenotype, that is, a mild, but significant, increase in tibial trabecular number and volume, and a sharp decrease in trabecular separation
• vision/eye phenotype
• *normal* vision/eye phenotype (MGI Ref ID J:82606)
  • homozygotes showed no anterior segment defects: the angle was open, and the depth of the anterior chamber appeared normal
• ocular hypertension (MGI Ref ID J:82606)
  • homozygotes showed a significant increase in mean intraocular pressure at 18, 24, and 36 weeks (21%, 44%, and 36%, respectively)
  • homozygotes displayed an increased accumulation of collagen I in conjunctiva, subconjunctival tissue, and sclera, suggesting an association between IOP regulation and fibrillar collagen turnover
• immune system phenotype
• abnormal osteoclast physiology (MGI Ref ID J:53079)
  • in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts
  • the bone resorption area and the number of osteoclasts/mm2 were significantly increased (~5-fold) after PTH injection in wild-type, but not in homozygous mutant mice
  • homozygotes were not resistant to other skeletal effects of PTH
  • after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type

View Research Applications

Research Applications

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

Col1a1^tm1Jae related

Cardiovascular Research
Heart Abnormalities (cardiomyopathy)

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Defects in Extracellular Matrix Molecules
Skeletal Defects

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Col1a1tm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-in)
Common Name(s)		Col1a1r; mutation IV; rr;
Mutation Made By		Rudolf Jaenisch,   Massachusetts Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Col1a1, collagen, type I, alpha 1
Chromosome		11
Gene Common Name(s)		COLIA1; Col1a-1; Cola-1; Cola1; Moloney leukemia virus 13; Mov-13; OI4;
Molecular Note		Several point mutations were introduced into the sequences encoding the collagenase cleavage domain by a "hit and run" targeting strategy. These mutations resulted in substitutions of proline for glutamine-774 and alanine-777 and methionine for isoleucine-776 in the encoded protein. [MGI Ref ID J:17514]

Genotyping

Genotyping Information

Genotyping Protocols

Cola1^tm1Jae, REST, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Liu X; Wu H; Byrne M; Jeffrey J; Krane S; Jaenisch R. 1995. A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. J Cell Biol 130(1):227-37. [PubMed: 7790374]  [MGI Ref ID J:26504]

Additional References

Aihara M; Lindsey JD; Weinreb RN. 2003. Ocular hypertension in mice with a targeted type I collagen mutation. Invest Ophthalmol Vis Sci 44(4):1581-5. [PubMed: 12657595]  [MGI Ref ID J:82606]

Mabuchi F; Lindsey JD; Aihara M; Mackey MR; Weinreb RN. 2004. Optic nerve damage in mice with a targeted type I collagen mutation. Invest Ophthalmol Vis Sci 45(6):1841-5. [PubMed: 15161848]  [MGI Ref ID J:92285]

Col1a1^tm1Jae related

Aihara M; Lindsey JD; Weinreb RN. 2003. Ocular hypertension in mice with a targeted type I collagen mutation. Invest Ophthalmol Vis Sci 44(4):1581-5. [PubMed: 12657595]  [MGI Ref ID J:82606]

Beare AH; Krane SM; Ferguson MW. 2005. Variable impairment of wound healing in the heterozygous collagenase-resistant mouse. Wound Repair Regen 13(1):27-40. [PubMed: 15659034]  [MGI Ref ID J:110086]

Chiusaroli R; Maier A; Knight MC; Byrne M; Calvi LM; Baron R; Krane SM; Schipani E. 2003. Collagenase cleavage of type I collagen is essential for both basal and parathyroid hormone (PTH)/PTH-related peptide receptor-induced osteoclast activation and has differential effects on discrete bone compartments. Endocrinology 144(9):4106-16. [PubMed: 12933685]  [MGI Ref ID J:85591]

Egeblad M; Shen HC; Behonick DJ; Wilmes L; Eichten A; Korets LV; Kheradmand F; Werb Z; Coussens LM. 2007. Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development. Dev Dyn 236(6):1683-93. [PubMed: 17440987]  [MGI Ref ID J:121546]

Lin M; Jackson P; Tester AM; Diaconu E; Overall CM; Blalock JE; Pearlman E. 2008. Matrix metalloproteinase-8 facilitates neutrophil migration through the corneal stromal matrix by collagen degradation and production of the chemotactic peptide Pro-Gly-Pro. Am J Pathol 173(1):144-53. [PubMed: 18556780]  [MGI Ref ID J:137367]

Lindsey ML; Yoshioka J; MacGillivray C; Muangman S; Gannon J; Verghese A; Aikawa M; Libby P; Krane SM; Lee RT. 2003. Effect of a cleavage-resistant collagen mutation on left ventricular remodeling. Circ Res 93(3):238-45. [PubMed: 12855673]  [MGI Ref ID J:115673]

Mabuchi F; Lindsey JD; Aihara M; Mackey MR; Weinreb RN. 2004. Optic nerve damage in mice with a targeted type I collagen mutation. Invest Ophthalmol Vis Sci 45(6):1841-5. [PubMed: 15161848]  [MGI Ref ID J:92285]

Provenzano PP; Inman DR; Eliceiri KW; Knittel JG; Yan L; Rueden CT; White JG; Keely PJ. 2008. Collagen density promotes mammary tumor initiation and progression. BMC Med 6:11. [PubMed: 18442412]  [MGI Ref ID J:138535]

Wu H; Liu X; Jaenisch R. 1994. Double replacement: strategy for efficient introduction of subtle mutations into the murine Col1a-1 gene by homologous recombination in embryonic stem cells. Proc Natl Acad Sci U S A 91(7):2819-23. [PubMed: 8146196]  [MGI Ref ID J:17514]

Zhao W; Byrne MH; Boyce BF; Krane SM. 1999. Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice. J Clin Invest 103(4):517-24. [PubMed: 10021460]  [MGI Ref ID J:53079]

Zhao W; Byrne MH; Wang Y; Krane SM. 2000. Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen. J Clin Invest 106(8):941-9. [PubMed: 11032854]  [MGI Ref ID J:90884]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.