Description

Strain Information

Former Names DW/J-acd/J    (Changed: 14-MAR-05 ) Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse

Appearance
leaden agouti, normal size
Related Genotype: A/A Mlph^ln/Mlph^ln ?/+

darkly pigmented, sparse coat, curly short whiskers, some with tail kinks or hind foot polydactlyly
Related Genotype: A/A Mlph^ln/Mlph^ln Acd^acd/Acd^acd

Description
acd/acd homozygotes can be distinguished from their wildtype (?/+) littermates by darkened pigmentation, short, curly vibrissae, smaller overall size, and abnormal pelage. Hair growth is retarded and lacks zigzag and guard hairs producing a sparse coat. There is heavy pigmentation in the nose, ears, body, feet and tail, and foci of melanin are also found in the skin and lymph nodes. Tail kinks or polydactyly of the hind feet are sometimes found and external genitalia are underdeveloped. It is rare for homozygotes to breed. Hydronephrosis is sometimes found in post-wean aged homozygotes resulting from focal hypertrophy of ureteral epithelium which causes ureteral blockage. The adrenals are abnormal in both males and females. Although the size of the medullary cells is normal, the cortical cells and nuclei are much larger than normal with nuclear inclusions and many mitochondria in the cytoplasm. These mitochondria have tubular cristae and cholesterol ester droplets, which are indicative of steroidogenic cells. The juxtamedullary X-zone of the adrenals is absent. The plasma levels of adrenocortical trophic hormone are elevated, and in young females, but not males, serum coticosterone levels are lower. FACS analysis reveals increased ploidy in many tissues. Adrenals show twice the number of tetraploid cells as is found in wildtype controls, and also an increase in the percent of cells with a higher than tetraploid DNA content. Spleen and thymus cells from newborns also show increased ploidy and a small percentage of cells with increased ploidy is found in cardiac muscle. Fewer mitotic figures and an uptake of tritiated thymidine into the enlarged nuclei indicate a failure in the normal mitotic pathway subsequent to S-phase. acd/acd homozygotes have significantly reduced viability. Approximately 40% die within 24 hours of birth and more than half of the homozygotes weaned die before 10 weeks of age. These mutants are much smaller at birth than wildtype siblings and this disparity in relative weights increases with age. Few homozygotes survive beyond six months of age. (Sweet et al., 1988; Shire and Beamer, 1990; Beamer et al., 1994.)

Development
The acd mutation arose spontaneously in the DW/J colony at The Jackson Laboratory in 1985. The Pit1^dw mutation was bred out of this substrain of DW/J and in 1994 ?/+ females at F26 were bred with acd/+ males to generate embryos for cryopreservation.

Control Information

	Control
	Untyped from the colony
Considerations for Choosing Controls

Additional Web Information

JAX^® NOTES, April 1988; 433. H-2 Haplotypes of Mice from Jackson Laboratory Production Colonies.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Acd^acd/Acd^acd

        involves: DW/J

• life span-post-weaning/aging
• premature death (MGI Ref ID J:14144)
  • none live beyond 6 months of age
• pigmentation phenotype
• abnormal ear pigmentation (MGI Ref ID J:14144)
  • heavy ear pigmentation
• hyperpigmentation (MGI Ref ID J:14144)
  • heavy pigmentation of ears, snout, body, feet, and tail
• endocrine/exocrine gland phenotype
• abnormal adrenal gland morphology (MGI Ref ID J:14144)
• hearing/vestibular/ear phenotype
• abnormal ear pigmentation (MGI Ref ID J:14144)
  • heavy ear pigmentation
• limbs/digits/tail phenotype
• kinked tail (MGI Ref ID J:14144)
  • noticeable at birth
• polydactyly (MGI Ref ID J:14144)
  • polydactyly of the rear feet noticeable at birth
• renal/urinary system phenotype
• abnormal kidney morphology (MGI Ref ID J:14144)
• reproductive system phenotype
• reduced fertility (MGI Ref ID J:14144)
• skin/coat/nails phenotype
• abnormal ear pigmentation (MGI Ref ID J:14144)
  • heavy ear pigmentation
• abnormal hair texture (MGI Ref ID J:14144)
• retarded hair growth (MGI Ref ID J:14144)
• sparse hair (MGI Ref ID J:14144)
• touch/vibrissae phenotype
• curly vibrissae (MGI Ref ID J:14144)
• short vibrissae (MGI Ref ID J:14144)
• craniofacial phenotype
• abnormal ear pigmentation (MGI Ref ID J:14144)
  • heavy ear pigmentation

Acd^acd/Acd^acd Pou1f1⁺/Pou1f1⁺

        DW/J

• endocrine/exocrine gland phenotype
• abnormal adrenal gland morphology (MGI Ref ID J:18027)
• small adrenal glands (MGI Ref ID J:18027)
• adrenal gland hypoplasia (MGI Ref ID J:18027)
  • majority of cells have enlarged nuclei
• homeostasis/metabolism phenotype
• abnormal corticosterone level (MGI Ref ID J:18027)
• decreased circulating corticosterone level (MGI Ref ID J:18027)
• abnormal pituitary hormone level (MGI Ref ID J:18027)
• abnormal adrenocorticotropin level (MGI Ref ID J:18027)
• increased adrenocorticotropin level (MGI Ref ID J:18027)

View Research Applications

Research Applications

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

Acd^acd related

Cell Biology Research
Cell Cycle Regulation
Genes Regulating Growth and Proliferation

Dermatology Research
Color and White Spotting Defects
Skin and Hair Texture Defects

Developmental Biology Research
Embryonic Lethality (Homozygous) (incomplete)
Growth Defects Growth Defects (homozygous)
Internal/Organ Defects (adrenal cortex)
Internal/Organ Defects (kidney)
Perinatal Lethality (Homozygous)
Postnatal Mortality (Homozygous)
Skin and Hair Texture Defects

Endocrine Deficiency Research
Adrenal Cortex Defects (Addison's disease)
Gonad Defects
Skin Defects

Internal/Organ Research
Adrenal Cortex Defects
Kidney Defects

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Acdacd
Allele Name		adrenocortical dysplasia
Allele Type		Spontaneous
Strain of Origin		DW/J
Gene Symbol and Name		Acd, adrenocortical dysplasia
Chromosome		8
Gene Common Name(s)		MGC116400; PIP1; PTOP; TINT1; TPP1;
Molecular Note		This spontaneous mutation arose at The Jackson Laboratory in 1985. A point mutation (G to A) in the +5 position of the splice donor site in the third intron of the gene was revealed by DNA sequence analysis. RT-PCR analysis showed that aberrant transcripts were expressed from this allele, all of which are predicted to alter the reading frame of the protein. [MGI Ref ID J:95686]

Genotyping

Genotyping Information

Genotyping Protocols

Acd^acd, EP, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Beamer WG; Sweet HO; Bronson RT; Shire JG; Orth DN; Davisson MT. 1994. Adrenocortical dysplasia: a mouse model system for adrenocortical insufficiency. J Endocrinol 141(1):33-43. [PubMed: 8014601]  [MGI Ref ID J:18027]

Acd^acd related

Beamer WG; Sweet HO; Bronson RT; Shire JG; Orth DN; Davisson MT. 1994. Adrenocortical dysplasia: a mouse model system for adrenocortical insufficiency. J Endocrinol 141(1):33-43. [PubMed: 8014601]  [MGI Ref ID J:18027]

Keegan CE; Hutz JE; Else T; Adamska M; Shah SP; Kent AE; Howes JM; Beamer WG; Hammer GD. 2005. Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator. Hum Mol Genet 14(1):113-23. [PubMed: 15537664]  [MGI Ref ID J:95686]

Sundberg JP (ed.). 1994. . In: Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. CRC Press, Boca Raton.  [MGI Ref ID J:30359]

Sweet HO; Beamer WG; Bronson RT. 1988. Adrenocortical dysplasia (acd). Mouse News Lett 81:69.  [MGI Ref ID J:14144]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Untyped from the colony
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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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

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