Overview

Also Known As:dark-like

These mice carry a spontaneous mutation at the Pepd locus characterized by a darkened coat color, smaller size, gonad abnormalities, and dark staining urine.

Genetic overview

Genetic Background	Generation

Pepd^dal

Allele Type	Gene Symbol	Gene Name
Spontaneous (Hypomorph)	Pepd	peptidase D

View Genetics

Research Applications

Reproductive Biology Research
Dermatology Research
Developmental Biology Research
Internal/Organ Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Dark-like dal is a recessive mutation causing a darkened coat color, smaller size, gonad abnormalities, and dark staining urine. dal maps to Chromosome 7 and a previously described mutation named dark da maps to the same chromosomal region. Dark-like may be a remutation to dark da.However a test for allelism is not possible because dark is thought to be extinct. Mice homozygous for the dal mutation are easily recognized by 14 days of age by their darkened coats and smaller size. Some homozygotes appear, both phenotypically and pathologically (dense bones), to have skeletal abnormalities however X-rays appear normal. At 7 months of age females had no follicles and many corpora lutea and males mild testicular degeneration with increased Leydig cells. Serum assays for Albumin, BUN, Creatine, Bilirubin, and iron showed no significant differences from controls.

Development

dal arose spontaneously in 1981 in the CBA/J colony of Dr. Eva Eicher at The Jackson Laboratory. The CBA/J colony was then at F182. This strain has been maintained via sibling mating and in 2004 reached F182+F72. Embryos were generated for cryopreservation using F182+52+ homozygous males bred with CBA/J females.

Control Suggestions

Heterozygote from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Harris BS; Ward-Bailey PF; Johnson KR; Eicher EM; Washburn LL; Gagnon LH; Bronson R. 2003. A new recessive coat color mutation on mouse Chromosome 7, dark-like. Mouse Mutant Resources Web Site, The Jackson Laboratory, Bar Harbor, Maine MGI Direct Data SubmissionMGI: J:87005
Jung S; Silvius D; Nolan KA; Borchert GL; Millet YH; Phang JM; Gunn TM. 2011. Developmental cardiac hypertrophy in a mouse model of prolidase deficiency. Birth Defects Res A Clin Mol Teratol 91(4):204-17PubMed: 21472842 MGI: J:215150

View All References

Genetics

Pepd^dal

Allele Symbol: Pepd^dal

Allele Name	dark-like
Allele Type	Spontaneous (Hypomorph)
Allele Synonym(s)
Gene Symbol and Name	Pepd, peptidase D
Gene Synonym(s)
Strain of Origin	CBA/J
Chromosome	7
Molecular Note	This spontaneous mutation is a 4 base pair deletion of ACTG in exon 14 that is predicted to cause a frameshift after amino acid 409 and replace the 84 carboxy terminal amino acids with 45 novel amino acids. QPCR shows a 42% decrease in expression in homozygous embryonic hearts and prolidase activity is reduced to undetectable levels in adult liver, E15.5 and adult heart, and adult red blood cells.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

hypertrophic cardiomyopathy

Research Areas By Phenotype

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

Genotype: Pepd^dal related

Reproductive Biology Research
- Developmental Defects Affecting Gonads
- Fertility Defects
Dermatology Research
- Color and White Spotting Defects
Developmental Biology Research
- Growth Defects
- Skeletal Defects
  - osteopetrosis
Internal/Organ Research
- Adrenal Cortex Defects
- Adrenal Medulla Defects

Internal/Organ Research
- Skeleton
  - Bone

Mammalian Phenotype Terms by Genotype

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

Genotype: Pepd^dal/Pepd^dal
involves: C3H/HeJ * CBA/J

cardiovascular system phenotype

abnormal aorta collagen fibril morphology
- dramatic reduction in the size and staining intensity of collagen fibrils in 2-month-old heart sections stained with picrosirius red

abnormal cardiac muscle tissue morphology

abnormal fetal cardiomyocyte morphology
- E15.5 beating cardiomyocytes are larger than normal

abnormal heart morphology

abnormal heart septum morphology
- atrial and ventricular septal defects are found in 17% of homozygous hearts between E12.5 and E18.5

abnormal myocardial fiber morphology
- at E15.5 there is a significant reduction in F-actin levels in the heart, and western blot analysis of cardiomyocytes also shows significant reduction in SRC, Tyr416 phosphorylated SRC, paxillin, and normal PTK2 expression but slighly reduced Tyr397 phosphorylated PTK2
- horylated PTK2
- myocytic and myofibrillar disarray can be found in 3 month old homozygotes, indicative of hypertrophic cardiomyopathy

atrioventricular septal defect

increased atrioventricular cushion size
- some homozygotes assessed between E12.5 and E18.5 have enlarged endocardial cushions but normal valves and atria

myocardium hypertrophy
- cardiomyocytes in the interventricular septum in cross sections from adult homozygotes and from E15.5 embryos are larger in diameter than normal and these sections show fewer cells per field of view than normal

thick interventricular septum
- in E15.5 homozygotes the interventricular septum at its midpoint is on average 1.6 fold thicker than normal

thick ventricular wall
- assessment of embryos between E12.5 and E18.5 shows significantly thickened ventricular walls and correspondingly smaller ventricular chambers in 68% of homozygotes

ventricular septal defect

embryo phenotype

embryonic growth retardation
- 8.1% of live embryos assessed between E10.5 and E18.5 are developmentally delayed

endocrine/exocrine gland phenotype

abnormal seminiferous tubule morphology

abnormal testis interstitial tissue morphology

abnormal testis morphology
- lipid rafts isolated from homozygous testes at 2 months of age appear normal by western blot for flotillin or caveolin but at 7 months of age they are weak or absent, perhaps as a consequence of vacuolation
- vacuoles are observed by histology of the testes within the seminiferous tubules and, to a lesser degree, in the interstitial region, first appearing between 1 and 3 months of age and become more numerous in older males

small testis
- testes from homozygotes tend to be smaller than normal

growth/size/body region phenotype

embryonic growth retardation
- 8.1% of live embryos assessed between E10.5 and E18.5 are developmentally delayed

myocardium hypertrophy
- cardiomyocytes in the interventricular septum in cross sections from adult homozygotes and from E15.5 embryos are larger in diameter than normal and these sections show fewer cells per field of view than normal

homeostasis/metabolism phenotype

decreased circulating testosterone level
- average serum testosterone levels at 3 months of age is lower than normal

decreased collagen level
- dramatic reduction in the size and staining intensity of collagen fibrils in 2-month-old heart sections stained with picrosirius red

integument phenotype

darkened coat color
- Background Sensitivity - homozygotes are darkest when young but retain a darkened coat relative to unaffected siblings as they age
- The darkened coat color that makes agouti appear more nonagouit except on the flanks is much darker on the C3H/HeJ mixed background than pure CBA/J

mortality/aging

postnatal lethality, incomplete penetrance
- many homozygotes are very small and die within 14 days of birth

prenatal lethality, incomplete penetrance
- fewer homozygotes than expected are produced from F1 heterozygous intercrosses and E10.5-E18.5 litters were found to have dead or resorbed embryos in 27% of implantation sites

muscle phenotype

abnormal cardiac muscle tissue morphology

abnormal myocardial fiber morphology
- at E15.5 there is a significant reduction in F-actin levels in the heart, and western blot analysis of cardiomyocytes also shows significant reduction in SRC, Tyr416 phosphorylated SRC, paxillin, and normal PTK2 expression but slighly reduced Tyr397 phosphorylated PTK2
- horylated PTK2
- myocytic and myofibrillar disarray can be found in 3 month old homozygotes, indicative of hypertrophic cardiomyopathy

myocardium hypertrophy
- cardiomyocytes in the interventricular septum in cross sections from adult homozygotes and from E15.5 embryos are larger in diameter than normal and these sections show fewer cells per field of view than normal

nervous system phenotype

brain vacuoles
- at 12 weeks of age 2 of 6 homozygotes display mild vacuolar changes in several regions of the brain including the thalamus, cortex, hippocampus, cerebellum, and pons

pigmentation phenotype

darkened coat color
- Background Sensitivity - homozygotes are darkest when young but retain a darkened coat relative to unaffected siblings as they age
- The darkened coat color that makes agouti appear more nonagouit except on the flanks is much darker on the C3H/HeJ mixed background than pure CBA/J

reproductive system phenotype

abnormal seminiferous tubule morphology

abnormal testis interstitial tissue morphology

abnormal testis morphology
- lipid rafts isolated from homozygous testes at 2 months of age appear normal by western blot for flotillin or caveolin but at 7 months of age they are weak or absent, perhaps as a consequence of vacuolation
- vacuoles are observed by histology of the testes within the seminiferous tubules and, to a lesser degree, in the interstitial region, first appearing between 1 and 3 months of age and become more numerous in older males

small testis
- testes from homozygotes tend to be smaller than normal

Genotype: Pepd^dal/Pepd^dal
involves: CAST/EiJ * CBA/J

growth/size/body region phenotype

decreased body size
- a smaller body size, most pronounced when young, occurs in approximately 36% (92 of 256) homozygotes in an N2 backcross population

integument phenotype

abnormal agouti pigmentation

darkened coat color
- only 397 of 410 homozygotes, from a heterozygote x homozygote intercross that produced 944 pups, were identified as having the darkened coat color indicating the presence of modifier genes impacting penetrance and expressivity

mortality/aging

preweaning lethality
- only 410 homozygotes were identified of 944 pups born in an N2 backcross population from (CAST/EiJ x CBA/J-dal homozygote)F1 x CBA/J-dal homozygote

pigmentation phenotype

abnormal agouti pigmentation

darkened coat color
- only 397 of 410 homozygotes, from a heterozygote x homozygote intercross that produced 944 pups, were identified as having the darkened coat color indicating the presence of modifier genes impacting penetrance and expressivity

Genotype: Pepd^dal/Pepd^dal Tg(Myh6/tetO-GCaMP2)1Mik/0
involves: C3H/HeJ C57BL/6J * CBA/J * DBA/2J

cardiovascular system phenotype

abnormal fetal cardiomyocyte physiology
- 43% of E12.5 dark-like homozygotes display abnormal calcium transients such as early after-depolarizations and interval irregularities, and those hearts that have these abnormalities also have thickened ventricular walls whereas those not displaying irregularities in calcium handling appeared normal
- ularities in calcium handling appeared normal

Genotype: Pepd^dal/Pepd^dal
involves: C3H/HeJ * C3HeB/FeJ * CBA/J

endocrine/exocrine gland phenotype

abnormal testis morphology
- ased to 9 out of 10 assessed
- at 3 months of age 13 out of 17 mice homozygous for dark-like on this background display significant vacuolation in the testes regardless of whether they are heterozgyous or wild-type for the mahogany 3 Jackson allele, and at 6 months of age this is increased to 9 out of 10 assessed

nervous system phenotype

brain vacuoles
- 2 of 5 homozygotes assessed at 2-3 months of age have mild vacuolation of the central nervous system

reproductive system phenotype

abnormal testis morphology
- ased to 9 out of 10 assessed
- at 3 months of age 13 out of 17 mice homozygous for dark-like on this background display significant vacuolation in the testes regardless of whether they are heterozgyous or wild-type for the mahogany 3 Jackson allele, and at 6 months of age this is increased to 9 out of 10 assessed

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

Genotype: Pepd^dal/Pepd^dal
CBA/J-Pepd/GrsrJ

cellular phenotype

decreased oocyte number
- by 7 months of age

reproductive system phenotype

decreased oocyte number
- by 7 months of age

growth/size/body region phenotype

decreased body size
- the effect on body size is variable with some homozygotes clearly smaller than normal and others not

homeostasis/metabolism phenotype

abnormal urine homeostasis
- dark-staining urine; the urine of mutants turns the pine-bedding shavings a darker yellow than normal, suggesting a metabolic defect

integument phenotype

darkened coat color
- Background Sensitivity - the darkened dorsal coat color on the CBA/J background becomes more subtle with age and are often indistinguishable from wildtype by 6 months of age

irregular coat pigmentation
- on an agouti background the yellow pigment characteristic of agouti is replaced by black on the back but not on the flanks

pigmentation phenotype

darkened coat color
- Background Sensitivity - the darkened dorsal coat color on the CBA/J background becomes more subtle with age and are often indistinguishable from wildtype by 6 months of age

irregular coat pigmentation
- on an agouti background the yellow pigment characteristic of agouti is replaced by black on the back but not on the flanks

renal/urinary system phenotype

abnormal urine homeostasis
- dark-staining urine; the urine of mutants turns the pine-bedding shavings a darker yellow than normal, suggesting a metabolic defect

References

Harris BS; Ward-Bailey PF; Johnson KR; Eicher EM; Washburn LL; Gagnon LH; Bronson R. 2003. A new recessive coat color mutation on mouse Chromosome 7, dark-like. Mouse Mutant Resources Web Site, The Jackson Laboratory, Bar Harbor, Maine MGI Direct Data SubmissionMGI: J:87005
Jung S; Silvius D; Nolan KA; Borchert GL; Millet YH; Phang JM; Gunn TM. 2011. Developmental cardiac hypertrophy in a mouse model of prolidase deficiency. Birth Defects Res A Clin Mol Teratol 91(4):204-17PubMed: 21472842 MGI: J:215150

Additional - Pepd^dal related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- small, dark agouti
  Related Genotype: A/A dal/dal
  
  agouti
  Related Genotype: A/A dal/+
Citation
When using the dark-like mouse strain in a publication, please cite the originating article(s) and include JAX stock #003398 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 for dal

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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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Also Known As:dark-like

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Pepddal

Allele Symbol: Pepddal

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: Pepddal related

Mammalian Phenotype Terms by Genotype

Genotype: Pepddal/Pepddalinvolves: C3H/HeJ * CBA/J

cardiovascular system phenotype

embryo phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

integument phenotype

mortality/aging

muscle phenotype

nervous system phenotype

pigmentation phenotype

reproductive system phenotype

Genotype: Pepddal/Pepddalinvolves: CAST/EiJ * CBA/J

growth/size/body region phenotype

integument phenotype

mortality/aging

pigmentation phenotype

Genotype: Pepddal/Pepddal Tg(Myh6*/tetO-GCaMP2)1Mik/0involves: C3H/HeJ * C57BL/6J * CBA/J * DBA/2J

cardiovascular system phenotype

Genotype: Pepddal/Pepddalinvolves: C3H/HeJ * C3HeB/FeJ * CBA/J

endocrine/exocrine gland phenotype

nervous system phenotype

reproductive system phenotype

Genotype: Pepddal/PepddalCBA/J-Pepd/GrsrJ

cellular phenotype

reproductive system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

integument phenotype

pigmentation phenotype

renal/urinary system phenotype

References

Additional - Pepddal 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

Pepd^dal

Allele Symbol: Pepd^dal

Genotype: Pepd^dal related

Genotype: Pepd^dal/Pepd^dal
involves: C3H/HeJ * CBA/J

Genotype: Pepd^dal/Pepd^dal
involves: CAST/EiJ * CBA/J

Genotype: Pepd^dal/Pepd^dal Tg(Myh6/tetO-GCaMP2)1Mik/0
involves: C3H/HeJ C57BL/6J * CBA/J * DBA/2J

Genotype: Pepd^dal/Pepd^dal
involves: C3H/HeJ * C3HeB/FeJ * CBA/J

Genotype: Pepd^dal/Pepd^dal
CBA/J-Pepd/GrsrJ

Additional - Pepd^dal related