Overview

This spontaneous mutation of the aggrecan (Acan) gene displays homozygous perinatal lethality, cleft palate, shortened long bones, tail and snout. Heterozygous mice exhibit spinal curvature followed by a premature death at 19 months. This strain may be useful in studies of spinal degeneration and achondroplasia.

Donating Investigator

Dr. Richard C. Krueger, Jr., University of New Mexico

Genetic overview

Genetic Background	Generation

Acan^cmd

Allele Type	Gene Symbol	Gene Name
Spontaneous	Acan	aggrecan

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Research Applications

Developmental Biology Research
Neurobiology Research
Endocrine Deficiency Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for this spontaneous mutation die just after birth from an in ability to breathe. Newborns exhibit cleft palate, a protruding tongue, bulging abdomen, enlarged liver and a shortened trunk, limbs, snout and tail. Long bones measure half the length of wild-type mice and the spinal column is reduced by 25%. Cartilage in homozygous mice consists of densely packed chrondocytes, little matrix, pycnotic cells and unusual amounts of collagen fibers.

Mice that are heterozygous for the mutation appear normal at birth, but develop proportional dwarfism by 28 days. Aging mice exhibit spinal misalignment and degeneration followed by the sudden onset of a spastic gait and an accompanying decrease in movement. Mice die within one month following the appearance of the abnormal gait. Heterozygotes do not live beyond 19 months.

This mutant mouse strain may be useful in studies of achondroplasia, disc herniation and spinal degeneration.

Development

The cartilage matrix deficiency (cmd) mutation arose spontaneously on a mouse stock with mutations in T, t^low and tf in the laboratory of Dr. Bennett at Memorial Sloan-Kettering Cancer Center in 1978. At some point, the strain was transferred to the NIH and then, to Dr. Richard Krueger at the University of New Mexico, Albuquerque. The strain was initially maintained by sibling matings and, then, at the University of New Mexico by outcrosses to mice with both C57BL/6 and BALB backgrounds. Dr. Krueger donated this strain to The Jackson Laboratory in 2009. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Rittenhouse E; Dunn LC; Cookingham J; Calo C; Spiegelman M; Dooher GB; Bennett D. 1978. Cartilage matrix deficiency (cmd): a new autosomal recessive lethal mutation in the mouse. J Embryol Exp Morphol 43:71-84PubMed: 632744 MGI: J:5952

View All References

Genetics

Acan^cmd

Allele Symbol: Acan^cmd

Allele Name	cartilage matrix deficiency
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Acan, aggrecan
Gene Synonym(s)
Strain of Origin	STOCK T t^low Itpr3^tf
Chromosome	7
Molecular Note	The molecular lesion is a 7 bp deletion in exon 5. Reduced mRNA levels are seen. The mutation disrupts the coding region corresponding to the B subdomain of the N-terminal globular G1 domain of the encoded protein, and introduces a frame-shift resulting in a truncated protein, if expressed.

Disease/Phenotype

Disease Terms

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).

achondroplasia

Research Areas By Phenotype

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

Developmental Biology Research
- Perinatal Lethality
  - Homozygous
- Growth Defects
- Craniofacial and Palate Defects
  - congenital cleft palate
Neurobiology Research
- Hearing Defects
Endocrine Deficiency Research
- Bone/Bone Marrow Defects
Mouse/Human Gene Homologs
- deafness

Mammalian Phenotype Terms by Genotype

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

Genotype: Acan^cmd/Acan⁺
involves: STOCK T t Itpr3

behavior/neurological phenotype

abnormal gait
- develop spastic gait and show decreased movement with sudden onset

aphagia
- mutants cannot eat and starve within 1 month of developing the abnormal gait

growth/size/body region phenotype

disproportionate dwarf
- slight dwarfism seen about 28 days after birth

mortality/aging

premature death
- no heterozygotes live longer than 19 months

nervous system phenotype

abnormal spinal cord morphology
- oppression of the spinal cord by herniated disk

skeleton phenotype

abnormal intervertebral disk morphology
- herniation of vertebral disks

abnormal vertebral body morphology
- disappearance of apophyseal cartilage and deformation of vertebral bodies

intervertebral disk degeneration
- the chondrocytes of vertebral disks show degeneration and are abnormally packed and the extracellular matrix shows concentric dense bundle patterns instead of a fine diffuse pattern

kyphosis
- in the thoraco-lumbar spine

lordosis
- in the cervical spine

Genotype: Acan^cmd/Acan^cmd
STOCK T t Itpr3

craniofacial phenotype

abnormal craniofacial bone morphology
- facial bones are reduced in antero-posterior length at E18

cleft palate

flattened snout
- snout is short and blunted

protruding tongue

short basicranium
- cranial base is reduced in antero-posterior length at E18

short snout

growth/size/body region phenotype

cleft palate

disproportionate dwarf
- noted at birth

distended abdomen
- abdomen is strikingly protruberant
- newborns display distended abdomens

enlarged liver
- liver is enlarged, likely due to congestion with blood

flattened snout
- snout is short and blunted

protruding tongue

short snout

limbs/digits/tail phenotype

abnormal limb morphology
- in E18 mutants, limb girdles and long bones are ~half of normal size
- mutants can be identified by E15 because of shortened limbs

absent caudal vertebrae
- number of tail vertebrae is reduced at E18

brachydactyly

short femur

short humerus

liver/biliary system phenotype

abnormal liver morphology
- in newborns, and to lesser extent in embryos, livers are darker than normal

enlarged liver
- liver is enlarged, likely due to congestion with blood

mortality/aging

neonatal lethality, complete penetrance
- homozygotes are born alive, but die shortly after birth due to inability to breathe

respiratory system phenotype

abnormal tracheal cartilage morphology
- chondrocytes are tightly packed, there is very little matrix and many pyknotic cells, which often contain vacuoles

respiratory distress

skeleton phenotype

abnormal cartilage development
- cartilage in all parts of skeleton is abnormal by E14
- cartilage shows reduced growth rate starting at ~E13

abnormal chondrocyte morphology
- in E16 limb bones, chondrocytes start to undergo degenerative changes
- mutant cells have few short and blunt cytoplasmic processes

abnormal craniofacial bone morphology
- facial bones are reduced in antero-posterior length at E18

abnormal rib morphology
- ribs are short and blunted at E18

abnormal trabecular bone morphology
- in E16 mutants, spongy bone is present throughout the width of the bone shaft, whereas in wild-type, it is confined to periosteum

abnormal tracheal cartilage morphology
- chondrocytes are tightly packed, there is very little matrix and many pyknotic cells, which often contain vacuoles

abnormal vertebrae morphology
- three calcification centers (one in vertebral body, one in each half of vertebral arch) are joined except in most posterior calcified vertebrae while these centers are well defined in the wild-type vertebrae

absent caudal vertebrae
- number of tail vertebrae is reduced at E18

decreased length of long bones
- long bones are reduced to >50% of normal length

short basicranium
- cranial base is reduced in antero-posterior length at E18

short femur

short humerus

short vertebral column
- axial skeleton is shortened at E18
- spinal column is shortened by ~25% (mutants 15.4 mm vs wild-type 21.4 mm in length)

digestive/alimentary phenotype

cleft palate

protruding tongue

Genotype: Acan^cmd/Acan^cmd
involves: STOCK T t Itpr3

craniofacial phenotype

cleft palate

homeostasis/metabolism phenotype

polyhydramnios
- volume of amniotic fluid is 8 times greater in mutants on E18

mortality/aging

neonatal lethality, complete penetrance
- die due to breathing failure just after birth

nervous system phenotype

abnormal cochlear IHC afferent innervation pattern
- no nerve fibers or nerve endings are observed in the first cochlear turn

abnormal cochlear inner hair cell morphology
- hair cells are fused

absent cochlear outer hair cells
- hair cells are absent in the first cochlear turn and in organ of Corti

respiratory system phenotype

abnormal lung morphology
- at E18, primary saccules are more numerous, appear compressed and parenchymal cells are less organized

pulmonary hypoplasia
- at E18, lungs are smaller than wild-type but normal in shape

digestive/alimentary phenotype

cleft palate

skeleton phenotype

abnormal cartilage development
- abnormally high fibronectin production by chrondrocytes results in aberrant cartilage
- in chondrocyte cultures, the defects in the cartilage produced can be ameliorated by the addition of cartilage proteoglycan monomer

growth/size/body region phenotype

cleft palate

disproportionate dwarf
- disproportionate, dwarfed stature
- short trunks, limbs, tails, snout

small thoracic cavity
- thoracic cavity volume is decreased by 38%

hearing/vestibular/ear phenotype

abnormal cochlear IHC afferent innervation pattern
- no nerve fibers or nerve endings are observed in the first cochlear turn

abnormal cochlear inner hair cell morphology
- hair cells are fused

abnormal organ of Corti morphology
- in organ of Corti, high density cystic formations are observed in Nuel's space and the tunnel of Corti

absent cochlear outer hair cells
- hair cells are absent in the first cochlear turn and in organ of Corti

deafness
- homozygotes display marked hearing loss

increased or absent threshold for auditory brainstem response
- responses can not be evoked with stimuli under 80 db

References

Rittenhouse E; Dunn LC; Cookingham J; Calo C; Spiegelman M; Dooher GB; Bennett D. 1978. Cartilage matrix deficiency (cmd): a new autosomal recessive lethal mutation in the mouse. J Embryol Exp Morphol 43:71-84PubMed: 632744 MGI: J:5952

Additional - Acan^cmd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Acan SEQ
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation die at birth.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Acan^cmd/NKruJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #010522 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
	Heterozygous or wildtype for Acan<cmd>

Related Products and Services

Frozen Mouse Embryo	STOCK Acan<cmd>/NKruJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Acan<cmd>/NKruJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Acan<cmd>/NKruJ Frozen Embryo	$3373.50
Frozen Mouse Embryo	STOCK Acan<cmd>/NKruJ Frozen Embryo	$3373.50

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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.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Acancmd

Allele Symbol: Acancmd

Disease Terms

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:

Mammalian Phenotype Terms by Genotype

Genotype: Acancmd/Acan+involves: STOCK T t Itpr3

behavior/neurological phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

Genotype: Acancmd/AcancmdSTOCK T t Itpr3

craniofacial phenotype

growth/size/body region phenotype

limbs/digits/tail phenotype

liver/biliary system phenotype

mortality/aging

respiratory system phenotype

skeleton phenotype

digestive/alimentary phenotype

Genotype: Acancmd/Acancmdinvolves: STOCK T t Itpr3

craniofacial phenotype

homeostasis/metabolism phenotype

mortality/aging

nervous system phenotype

respiratory system phenotype

digestive/alimentary phenotype

skeleton phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

References

Additional - Acancmd related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Acan^cmd

Allele Symbol: Acan^cmd

Genotype: Acan^cmd/Acan⁺
involves: STOCK T t Itpr3

Genotype: Acan^cmd/Acan^cmd
STOCK T t Itpr3

Genotype: Acan^cmd/Acan^cmd
involves: STOCK T t Itpr3

Additional - Acan^cmd related