Overview

This inbred mutant strain carries the congenital hydrocephalus (Foxc1^ch) and muted (Bloc1s5^mu) mutations characterized by light eyes at birth and a muted brown shade of fur, and various abnormalities including hydrocephalus.

Genetic overview

Genetic Background	Generation

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Research Applications

Dermatology Research
Neurobiology Research
Sensorineural Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Important Note

This strain is heterozygous for Foxc1^ch and Bloc1s5^mu maintained in repulsion.

Detailed Description

Mice homozygous for the congenital hydrocephalus (Foxc1^ch) spontaneous mutation die at birth, probably from inability to breathe. Homozygous mutant mice have bulging hemorrhagic cerebral hemispheres and open eyelids, urogenital abnormalities, and severely abnormal skull, cervical vertebrae, sternum, laryngeal cartilages, and hyoid bone. The hydrocephalus may trace to lack of formation of subarachnoid space, which is first detectable in 11-day embryos. Most of the defects in the head region are probably secondary to the severe displacements created by the hydrocephalus. Mice homozygous for the muted spontaneous mutation (Bloc1s5^mu), maintained in repulsion with congenital hydrocephalus, have light eyes at birth and their fur is a muted brown shade, often with white underfur. Some have a balance defect, similar to that of pallid (Bloc1s6^pa). Homozygous mutant mice show head-tilting and loss of postural reflexes, due to absence of otoliths from the sacculus and utriculus of one or both ears. The bony labyrinth is normal; the mice are not deaf and do not circle. Mutant mice have prolonged bleeding times and a platelet storage pool deficiency (SPD) associated with abnormalities of the dense granules of the blood platelets.

Control Suggestions

? +/+ ? untested from colony

Additional Information

Considerations for Choosing Controls

Selected References

Lyon MF; Meredith R. 1969. Muted, a new mutant affecting coat colour and otoliths of the mouse, and its position in linkage group XIV. Genet Res 14(2):163-6PubMed: 5367369 MGI: J:5145

View All References

Genetics

Bloc1s5^mu

Allele Symbol: Bloc1s5^mu

Allele Name	muted
Allele Type	Spontaneous (Hypomorph)
Allele Synonym(s)	mu
Gene Symbol and Name	Bloc1s5, biogenesis of lysosomal organelles complex-1, subunit 5, muted
Gene Synonym(s)
Strain of Origin	STOCK t
Chromosome	13
Molecular Note	An early transposon (Etn) insertion has been identified as the mutation underlying the phenotype in muted mice. Analysis of genomic DNA revealed an insertion into the third intron. 183 bp of Etn sequence has been incorporated into the mRNA , likely by the activation of cryptic splice sites within the Etn. This results in an in-frame insertion into the translated protein at position 106, predicting a 246 amino acid protein. A significant reduction in mRNA levels is observed.

Foxc1^ch

Allele Symbol: Foxc1^ch

Allele Name	congenital hydrocephalus
Allele Type	Spontaneous
Allele Synonym(s)	ch; mf1^ch
Gene Symbol and Name	Foxc1, forkhead box C1
Gene Synonym(s)
Strain of Origin	CBA x STOCK Tyr^c f
Chromosome	13
Molecular Note	A transition point mutation at coding nucleotide 367 altered a C to a T in the coding region. This results in a stop codon in place of glutamine codon 123 (p.Q123*) in the sequences encoding the third helix of the WH domain. The authors predict that a truncated protein would be generated lacking DNA binding activity.

Disease/Phenotype

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:

Genotype: Bloc1s5^mu related

Dermatology Research
- Color and White Spotting Defects
Neurobiology Research
- Hearing Defects
Sensorineural Research
- Hearing Defects

Genotype: Foxc1^ch related

Developmental Biology Research
- Neurodevelopmental Defects
- Craniofacial and Palate Defects
  - hydrocephaly: severely abnormal skull
- Skeletal Defects
  - hydrocephaly
Neurobiology Research
- Neurodevelopmental Defects
Sensorineural Research
- Eye Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Foxc1^ch/Foxc1⁺
involves: CBA * STOCK Tyr f

cardiovascular system phenotype

abnormal kidney blood vessel morphology
- abnormal arrangement of the renal arteries and veins may be seen at P0 but with a lower incidence compared to homozygotes

abnormal right renal artery morphology
- at 4 weeks of age about 50% of mice have an abnormal right renal artery

reproductive system phenotype

abnormal reproductive system morphology
- at 4 weeks of age about 1/6 of mice have urogenital abnormalities

ectopic ovary
- may be located more anteriorly than in controls
- this occurs with a lower incidence compared to homozygotes

ectopic testis
- may be located more anteriorly than in controls
- this occurs with a lower incidence compared to homozygotes

respiratory system phenotype

abnormal thyroid cartilage morphology
- may have defects on the ventral side

skeleton phenotype

abnormal cervical atlas morphology
- the neural canal is wider and more rounded at its ventral border and the lateral vertebral foramen is often open dorsolaterally

abnormal foramen magnum morphology
- the border of the foramen magnum at the suture between the supraoccipital and exoccipital is slightly concave rather than straight or slightly convex as in controls

abnormal sternum morphology
- in some mice at 4 weeks of age, the anterior and posterior halves of the sternum consist of separate bones

abnormal thyroid cartilage morphology
- may have defects on the ventral side

craniofacial phenotype

abnormal foramen magnum morphology
- the border of the foramen magnum at the suture between the supraoccipital and exoccipital is slightly concave rather than straight or slightly convex as in controls

endocrine/exocrine gland phenotype

ectopic ovary
- may be located more anteriorly than in controls
- this occurs with a lower incidence compared to homozygotes

ectopic testis
- may be located more anteriorly than in controls
- this occurs with a lower incidence compared to homozygotes

mammalian phenotype

nervous system phenotype
- Normal - unlike homozygotes, no cases of hydrocephalus are seen

renal/urinary system phenotype

abnormal kidney blood vessel morphology
- abnormal arrangement of the renal arteries and veins may be seen at P0 but with a lower incidence compared to homozygotes

abnormal renal/urinary system morphology
- at 4 weeks of age about 1/6 of mice have urogenital abnormalities

abnormal right renal artery morphology
- at 4 weeks of age about 50% of mice have an abnormal right renal artery

hydronephrosis
- incidence is less than that in homozygotes

hydroureter
- incidence is less than that in homozygotes

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

Genotype: Bloc1s5^mu/Bloc1s5^mu
CHMU/Le

cellular phenotype

decreased lysosomal enzyme secretion
- lysosomal enzyme levels are increased in kidneys and there is an associated decrease in secretion into the urine
- thrombin induced release of glucuronidase from platelets is decreased, although to a lesser degree than in mocha homozygotes, and thrombin induced release of galactosidase is 60% to 70% of normal

mammalian phenotype

hematopoietic system phenotype
- Normal - normal platelet counts

nervous system phenotype

decreased platelet serotonin level
- platelet serotonin levels are less than 8% those of normal

pigmentation phenotype

abnormal melanosome morphology
- choroidal melanosomes often are less dense and may exhibit irregular outlines
- remaining retinal pigment epithelium melanosomes are smaller and often contain unusual inclusions and lamellar bodies
- total numbers of melanosomes are reduced severely within the retinal pigment epithelium and within the choroid in adults

abnormal retinal pigment epithelium morphology
- although homozygotes do not have the giant granules that are found in the retinal pigment epithelial cells of beige mice, they do have enlarged retinal pigment granules

decreased eye pigmentation
- hypopigmentation of the eyes is seen in young (less than 5 days of age) mice

hypopigmentation
- hypopigmentation of the coat, with fur or a light muted brown shade

renal/urinary system phenotype

abnormal proximal convoluted tubule morphology
- higher than normal autofluorescence, typical of ceroid-like pigment, is found in proximal tubules

vision/eye phenotype

abnormal retinal pigment epithelium morphology
- although homozygotes do not have the giant granules that are found in the retinal pigment epithelial cells of beige mice, they do have enlarged retinal pigment granules

decreased eye pigmentation
- hypopigmentation of the eyes is seen in young (less than 5 days of age) mice

hematopoietic system phenotype

abnormal platelet dense granule morphology
- although a normal number of dense granules stain with mepacrine, UV flashing is reduced by more than fivefold indicating an abnormal intragranular environment

abnormal platelet dense granule physiology
- very little releasable ATP is detected when low or high levels of collagen are added to platelets from homozygotes

decreased platelet aggregation
- decreased aggregation both in the presence of high or low concentrations of collagen

decreased platelet dense granule number
- platelets nearly devoid of dense granules

decreased platelet serotonin level
- platelet serotonin levels are less than 8% those of normal

homeostasis/metabolism phenotype

abnormal platelet dense granule physiology
- very little releasable ATP is detected when low or high levels of collagen are added to platelets from homozygotes

decreased platelet aggregation
- decreased aggregation both in the presence of high or low concentrations of collagen

decreased platelet serotonin level
- platelet serotonin levels are less than 8% those of normal

increased bleeding time
- bleed time is greater than 15 minutes

Genotype: Foxc1^ch/Foxc1⁺
CHMU/Le

cardiovascular system phenotype

corneal vascularization
- present in some older mice

mammalian phenotype

vision/eye phenotype
- Normal - despite these abnormalities intraocular pressure is rarely increased

vision/eye phenotype

abnormal anterior eye segment morphology
- 48 of 51 had clinically detectable abnormalities with 40 mice having bilateral abnormalities

abnormal canal of Schlemm morphology
- small or absent

abnormal ciliary process morphology
- short and thin ciliary processes in some mice

abnormal iridocorneal angle
- abnormalities include large blood vessels and iris strands
- most eyes contain morphologically normal and abnormal regions of the iridocorneal angle

abnormal trabecular meshwork morphology
- areas may be hypoplastic or absent
- in some places the trabecular meshwork appears compressed
- some areas where the trabecular meshwork is absent contain cells that resemble mesenchymal precursor cells

absent Schlemm's canal
- small or absent

anterior iris synechia
- tend to be more severe than in Foxc1^tm1Blh heterozygotes on a C57BL/6J containing background

cataract
- seen in about 25% of mice and the incidence increase with age

ciliary body hypoplasia
- some eyes have a focally hypoplastic ciliary body with short and thin ciliary processes

corneal vascularization
- present in some older mice

mydriasis
- some have very large pupils resembling the phenotype associated with aniridia

Genotype: Foxc1^ch/Foxc1^ch
CHMU/LeJ

growth/size/body region phenotype

decreased fetal size
- slight dwarf phenotype at E15.5

limbs/digits/tail phenotype

short limbs

skeleton phenotype

abnormal sternocostal joint morphology
- disorganized rib fusion to the sternum

abnormal vertebrae development
- calcification of vertebrae is impaired in newborns

delayed endochondral bone ossification
- degradation of the hypertrophic chondrocyte zone in the center of tibias is not seen at E15.5 as in wild-type tibias
- newborns show smaller ossification centers in the femurs and tibias and smaller ossification areas are already seen at E15.5

failure of sternum ossification
- sternum of newborns shows complete absence of hypertrophic chondrocytes and ossification

increased width of hypertrophic chondrocyte zone
- the hypertrophic chondrocyte zone of tibial growth plate is longer

Phenotype Information

References

Lyon MF; Meredith R. 1969. Muted, a new mutant affecting coat colour and otoliths of the mouse, and its position in linkage group XIV. Genet Res 14(2):163-6PubMed: 5367369 MGI: J:5145

Additional References

Green MC. 1970. The developmental effects of congenital hydrocephalus (ch) in the mouse. Dev Biol 23(4):585-608PubMed: 5500588 MGI: J:5191
Jones SM; Erway LC; Johnson KR; Yu H; Jones TA. 2004. Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191(1-2):34-40PubMed: 15109702 MGI: J:89392
Kume T; Deng K; Hogan BL. 2000. Murine forkhead/winged helix genes Foxc1 (Mf1) and Foxc2 (Mfh1) are required for the early organogenesis of the kidney and urinary tract. Development 127(7):1387-95PubMed: 10704385 MGI: J:60834
Rice R; Rice DP; Olsen BR; Thesleff I. 2003. Progression of calvarial bone development requires Foxc1 regulation of Msx2 and Alx4. Dev Biol 262(1):75-87PubMed: 14512019 MGI: J:85739
Smith RS; Zabaleta A; Kume T; Savinova OV; Kidson SH; Martin JE; Nishimura DY; Alward WL; Hogan BL; John SW. 2000. Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development. Hum Mol Genet 9(7):1021-32PubMed: 10767326 MGI: J:61775
Swank RT; Reddington M; Howlett O; Novak EK. 1991. Platelet storage pool deficiency associated with inherited abnormalities of the inner ear in the mouse pigment mutants muted and mocha. Blood 78(8):2036-44PubMed: 1912584 MGI: J:29151
Zhang Q; Li W; Novak EK; Karim A; Mishra VS; Kingsmore SF; Roe BA; Suzuki T; Swank RT. 2002. The gene for the muted (mu) mouse, a model for Hermansky-Pudlak syndrome, defines a novel protein which regulates vesicle trafficking. Hum Mol Genet 11(6):697-706PubMed: 11912185 MGI: J:75830

Additional - Bloc1s5^mu related

Additional - Foxc1^ch related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- muted brown shade, possible head tilt
  Related Genotype: A/A Bloc1s5^mu +/Bloc1s5^mu ?
  
  agouti, unaffected
  Related Genotype: A/A + ?/? + or A/A Foxc1^ch +/+ Bloc1s5^mu
Citation
When using the CHMU/LeJ mouse strain in a publication, please include JAX stock #000293 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
	Genes in Repulsion: Heterozygous for Foxc1<ch>, Heterozygous for Muted<mu>

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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.

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Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Control Suggestions

Additional Information

Selected References

Bloc1s5mu

Allele Symbol: Bloc1s5mu

Foxc1ch

Allele Symbol: Foxc1ch

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:

Genotype: Bloc1s5mu related

Genotype: Foxc1ch related

Mammalian Phenotype Terms by Genotype

Genotype: Foxc1ch/Foxc1+involves: CBA * STOCK Tyr f

cardiovascular system phenotype

reproductive system phenotype

respiratory system phenotype

skeleton phenotype

craniofacial phenotype

endocrine/exocrine gland phenotype

mammalian phenotype

renal/urinary system phenotype

Genotype: Bloc1s5mu/Bloc1s5muCHMU/Le

cellular phenotype

mammalian phenotype

nervous system phenotype

pigmentation phenotype

renal/urinary system phenotype

vision/eye phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Foxc1ch/Foxc1+CHMU/Le

cardiovascular system phenotype

mammalian phenotype

vision/eye phenotype

Genotype: Foxc1ch/Foxc1chCHMU/LeJ

growth/size/body region phenotype

limbs/digits/tail phenotype

skeleton phenotype

Phenotype Information

References

Additional References

Additional - Bloc1s5mu related

Additional - Foxc1ch related

Genotyping Protocols

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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Bloc1s5^mu

Allele Symbol: Bloc1s5^mu

Foxc1^ch

Allele Symbol: Foxc1^ch

Genotype: Bloc1s5^mu related

Genotype: Foxc1^ch related

Genotype: Foxc1^ch/Foxc1⁺
involves: CBA * STOCK Tyr f

Genotype: Bloc1s5^mu/Bloc1s5^mu
CHMU/Le

Genotype: Foxc1^ch/Foxc1⁺
CHMU/Le

Genotype: Foxc1^ch/Foxc1^ch
CHMU/LeJ

Additional - Bloc1s5^mu related

Additional - Foxc1^ch related