Col1a1<tm1Jae> Targeted Allele Detail MGI Mouse (MGI:1857154)

Col1a1^tm1Jae
Targeted Allele Detail

Nomenclature

Symbol:	Col1a1^tm1Jae
Name:	collagen, type I, alpha 1; targeted mutation 1, Rudolf Jaenisch
MGI ID:	MGI:1857154
Synonyms:	Col^R, Col1a1^r, mutation IV, rr
Gene:	Col1a1 Location: Chr11:94797538-94814356 bp, + strand Genetic Position: Chr11, 56.0 cM, cytoband D

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:26504
Parent Cell Line:	J1 (ES Cell)
Strain of Origin:	129S4/SvJae

Mutation
description

Allele Type:	Targeted (knock-in)
Mutations:	Insertion, Nucleotide substitutions
	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. (J:17514)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Col1a1 Mutation:	47 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	ht3
craniofacial			√
abnormal calvaria morphology			√
		hm1	hm2	ht3
growth/size			√
decreased body weight			√
		hm1	hm2	ht3
immune system			√
abnormal osteoclast physiology			√
		hm1	hm2	ht3
limbs/digits/tail			√
abnormal skeleton extremities morphology			√
		hm1	hm2	ht3
reproductive system		√		√
abnormal uterus morphology		√		√
abnormal myometrium morphology		√
decreased litter size		√		√
		hm1	hm2	ht3
skeleton			√
skeleton phenotype			N
abnormal calvaria morphology			√
abnormal osteoclast physiology			√
abnormal skeleton extremities morphology			√
abnormal osteoblast morphology			√
abnormal osteoblast differentiation			√
abnormal osteocyte morphology			√
osteopetrosis			√
abnormal joint morphology			√
failure of secondary bone resorption			√
		hm1	hm2	ht3
skin/coat/nails		√		√
partial hair loss		√		√
thick dermal layer		√		√
		hm1	hm2	ht3
vision/eye			√
vision/eye phenotype			N
ocular hypertension			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Col1a1^tm1Jae/Col1a1^tm1Jae	either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
reproductive system abnormal uterus morphology (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 abnormal myometrium morphology (J:26504) occasionally, virgin homozygous females showed small accumulations of collagen in the myometrium of the uterus decreased litter size (J:26504) mutant females had slightly reduced litter sizes and significantly fewer litters than wild-type females skin/coat/nails partial hair loss (J:26504) homozygotes developed patchy hair loss thick dermal layer (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
Genotype	Allelic Composition	Genetic Background
hm2	Col1a1^tm1Jae/Col1a1^tm1Jae	involves: 129S4/SvJae * C57BL/6
craniofacial abnormal calvaria morphology (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 decreased body weight (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 abnormal skeleton extremities morphology (J:53079) adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone skeleton skeleton phenotype (J:85591) homozygotes showed normal tooth eruption abnormal calvaria morphology (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 osteoclast physiology (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 (J:53079) adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone abnormal osteoblast morphology (J:90884) beginning at about 2 weeks of age, homozygotes showed increased osteoblast and osteocyte apoptosis, despite increased bone deposition abnormal osteoblast differentiation (J:85591, J:90884) at 4 weeks, homozygotes showed an increase in tibial trabecular bone volume despite an overall decrease in osteoblast activity in trabecular bone (J:85591) in contrast, homozygotes displayed normal tibial cortical bone thickness, and a relatively normal tibial periosteal mineral apposition rate (J:85591) at greater 4 weeks of age, mutants began to show increased bone deposition of endosteal trabecular bone in tibial/femoral bones (J:90884) abnormal osteocyte morphology (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 osteopetrosis (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 abnormal joint morphology (J:53079) adult homozygotes developed joint contractures failure of secondary bone resorption (J:85591) homozygotes showed impaired osteoclastic bone resorption in trabecular bone: namely, an increase in osteoclast number and surface in long bones vision/eye vision/eye phenotype (J:82606) homozygotes showed no anterior segment defects: the angle was open, and the depth of the anterior chamber appeared normal ocular hypertension (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 abnormal osteoclast physiology (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
Genotype	Allelic Composition	Genetic Background
ht3	Col1a1^tm1Jae/Col1a1⁺	either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
reproductive system abnormal uterus morphology (J:26504) collagen accumulation in the uteri of heterozygous mutants was less pronounced relative to homozygous mutants decreased litter size (J:26504) heterozygous females had slightly reduced litter sizes and significantly fewer litters than wild-type females skin/coat/nails partial hair loss (J:26504) heterozygotes developed patchy hair loss thick dermal layer (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

References

Original:	J:26504 Liu X et al., "A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling." J Cell Biol 1995 Jul;130(1):227-37
All:	14 reference(s)

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
Citing These Resources Funding Information Warranty Disclaimer & Copyright Notice Send questions and comments to User Support.	last database update 11/20/2009 MGI_4.31 Web browser compatibility