Phenotypes associated with this allele

• Allele Symbol: Pepd^dal
• Allele Name: dark-like
• Allele ID: MGI:2683249
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pepd^dal/Pepd^dal	CBA/J-Pepd^dal/GrsrJ	MGI:2683289
hm2	Pepd^dal/Pepd^dal	involves: C3H/HeJ * C3HeB/FeJ * CBA/J	MGI:5605680
hm3	Pepd^dal/Pepd^dal	involves: C3H/HeJ * CBA/J	MGI:5604775
hm4	Pepd^dal/Pepd^dal	involves: CAST/EiJ * CBA/J	MGI:5604801
cx5	Atrn^mg-3J/Atrn^+ Pepd^dal/Pepd^dal	involves: C3H/HeJ * C3HeB/FeJ * CBA/J	MGI:5605670
cx6	Atrn^mg-3J/Atrn^+ Pepd^dal/Pepd^+	involves: C3H/HeJ * C3HeB/FeJ * CBA/J	MGI:5605679
cx7	Pepd^dal/Pepd^dal Tg(Myh6*/tetO-GCaMP2)1Mik/0	involves: C3H/HeJ * C57BL/6J * CBA/J * DBA/2J	MGI:5604875
cx8	A^y/A Pepd^dal/Pepd^dal	involves: C3H/HeJ * CBA/J	MGI:5605663
cx9	Pepd^dal/Pepd^dal Tg(ACTB-Atrnl1)B4Tmg/0	involves: C57BL/6 * CBA/J * DBA/J	MGI:5605683
cx10	Mc1r^e/Mc1r^e Pepd^dal/Pepd^dal	involves: C57BL/6J * CBA/J	MGI:5605682

Genotype
MGI:2683289

hm1

• Allelic Composition: Pepd^dal/Pepd^dal
• Genetic Background: CBA/J-Pepd^dal/GrsrJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

8 day old Pepd^dal/Pepd^dal

pigmentation

darkened coat color ( J:143333 )

• 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 ( J:87005 )

• on an agouti background the yellow pigment characteristic of agouti is replaced by black on the back but not on the flanks

growth/size/body

decreased body size ( J:87005 , J:143333 )

• the effect on body size is variable with some homozygotes clearly smaller than normal and others not (J:143333)

homeostasis/metabolism

abnormal urine homeostasis ( J:87005 )

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

renal/urinary system

abnormal urine homeostasis ( J:87005 )

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

reproductive system

decreased oocyte number ( J:87005 )

♀ • by 7 months of age

integument

darkened coat color ( J:143333 )

• 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 ( J:87005 )

• on an agouti background the yellow pigment characteristic of agouti is replaced by black on the back but not on the flanks

cellular

decreased oocyte number ( J:87005 )

♀ • by 7 months of age

Genotype
MGI:5605680

hm2

• Allelic Composition: Pepd^dal/Pepd^dal
• Genetic Background: involves: C3H/HeJ * C3HeB/FeJ * CBA/J

endocrine/exocrine glands

abnormal testis morphology ( J:143333 )

♂ • 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

reproductive system

abnormal testis morphology ( J:143333 )

♂ • 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

brain vacuoles ( J:143333 )

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

Genotype
MGI:5604775

hm3

• Allelic Composition: Pepd^dal/Pepd^dal
• Genetic Background: involves: C3H/HeJ * CBA/J

homeostasis/metabolism

decreased circulating testosterone level ( J:143333 )

♂ • average serum testosterone levels at 3 months of age is lower than normal

decreased collagen level ( J:215150 )

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

cardiovascular system

abnormal aorta collagen fibril morphology ( J:215150 )

• 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 ( J:215150 )

abnormal heart morphology ( J:215150 )

abnormal myocardial fiber morphology ( J:215150 )

• myocytic and myofibrillar disarray can be found in 3 month old homozygotes, indicative of hypertrophic cardiomyopathy

• 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

myocardium hypertrophy ( J:215150 )

• 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

increased atrioventricular cushion size ( J:215150 )

• some homozygotes assessed between E12.5 and E18.5 have enlarged endocardial cushions but normal valves and atria

increased fetal cardiomyocyte size ( J:215150 )

• E15.5 beating cardiomyocytes are larger than normal

abnormal heart septum morphology ( J:215150 )

• atrial and ventricular septal defects are found in 17% of homozygous hearts between E12.5 and E18.5

atrioventricular septal defect ( J:215150 )

thick interventricular septum ( J:215150 )

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

ventricular septal defect ( J:215150 )

thick ventricular wall ( J:215150 )

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

muscle

abnormal cardiac muscle tissue morphology ( J:215150 )

abnormal myocardial fiber morphology ( J:215150 )

• myocytic and myofibrillar disarray can be found in 3 month old homozygotes, indicative of hypertrophic cardiomyopathy

• 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

myocardium hypertrophy ( J:215150 )

• 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

mortality/aging

postnatal lethality, incomplete penetrance ( J:215150 )

• many homozygotes are very small and die within 14 days of birth

prenatal lethality, incomplete penetrance ( J:215150 )

• 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

growth/size/body

myocardium hypertrophy ( J:215150 )

• 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

embryonic growth retardation ( J:215150 )

• 8.1% of live embryos assessed between E10.5 and E18.5 are developmentally delayed

embryo

embryonic growth retardation ( J:215150 )

• 8.1% of live embryos assessed between E10.5 and E18.5 are developmentally delayed

pigmentation

darkened coat color ( J:143333 , J:215150 )

• Background Sensitivity: homozygotes are darkest when young but retain a darkened coat relative to unaffected siblings as they age (J:143333)

• 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 (J:215150)

integument

darkened coat color ( J:143333 , J:215150 )

• Background Sensitivity: homozygotes are darkest when young but retain a darkened coat relative to unaffected siblings as they age (J:143333)

• 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 (J:215150)

endocrine/exocrine glands

abnormal testis morphology ( J:143333 )

♂ • 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

♂ • 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

abnormal seminiferous tubule morphology ( J:143333 )

♂

abnormal testis interstitial tissue morphology ( J:143333 )

♂

small testis ( J:143333 )

♂ • testes from homozygotes tend to be smaller than normal

reproductive system

abnormal testis morphology ( J:143333 )

♂ • 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

♂ • 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

abnormal seminiferous tubule morphology ( J:143333 )

♂

abnormal testis interstitial tissue morphology ( J:143333 )

♂

small testis ( J:143333 )

♂ • testes from homozygotes tend to be smaller than normal

nervous system

brain vacuoles ( J:143333 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy		DOID:11984		J:215150

Genotype
MGI:5604801

hm4

• Allelic Composition: Pepd^dal/Pepd^dal
• Genetic Background: involves: CAST/EiJ * CBA/J

integument

abnormal agouti pigmentation ( J:215150 )

darkened coat color ( J:215150 )

• 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

pigmentation

abnormal agouti pigmentation ( J:215150 )

darkened coat color ( J:215150 )

• 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 ( J:215150 )

• 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

growth/size/body

decreased body size ( J:143333 )

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

Genotype
MGI:5605670

cx5

• Allelic Composition: Atrn^mg-3J/Atrn⁺; Pepd^dal/Pepd^dal
• Genetic Background: involves: C3H/HeJ * C3HeB/FeJ * CBA/J

integument

darkened coat color ( J:143333 )

• mice homozygous for dark-like and heterozgyous for the mahogany 3 Jackson allele of attractin have a darker coat color than mice homozygous for dark-like and wildtype for attractin

pigmentation

darkened coat color ( J:143333 )

• mice homozygous for dark-like and heterozgyous for the mahogany 3 Jackson allele of attractin have a darker coat color than mice homozygous for dark-like and wildtype for attractin

endocrine/exocrine glands

abnormal testis morphology ( J:143333 )

♂ • 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

reproductive system

abnormal testis morphology ( J:143333 )

♂ • 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

brain vacuoles ( J:143333 )

• at 2-3 months of age no vacuoles are found in compound heterozgyotes, 2 of 5 dark-like homozygotes wild-type for attractin have vacuolation in multiple brain regions, while dark-like homozygotes heterozygous for mahogany 3 Jackson have a range of CNS vacuolation from undetectable to severe

Genotype
MGI:5605679

cx6

• Allelic Composition: Atrn^mg-3J/Atrn⁺; Pepd^dal/Pepd⁺
• Genetic Background: involves: C3H/HeJ * C3HeB/FeJ * CBA/J

endocrine/exocrine glands

abnormal testis morphology ( J:143333 )

♂ • indicative of an additive interaction of these alleles, both of two compound heterozygotes assessed at 3 months of age and 5 of 9 assessed at 6 months of age display vacuolation in the testes, although to a lesser degree than is found in dark-like homozygotes

reproductive system

abnormal testis morphology ( J:143333 )

♂ • indicative of an additive interaction of these alleles, both of two compound heterozygotes assessed at 3 months of age and 5 of 9 assessed at 6 months of age display vacuolation in the testes, although to a lesser degree than is found in dark-like homozygotes

Genotype
MGI:5604875

cx7

• Allelic Composition: Pepd^dal/Pepd^dal; Tg(Myh6*/tetO-GCaMP2)1Mik/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J * CBA/J * DBA/2J

cardiovascular system

abnormal fetal cardiomyocyte physiology ( J:215150 )

• 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

Genotype
MGI:5605663

cx8

• Allelic Composition: A^y/A; Pepd^dal/Pepd^dal
• Genetic Background: involves: C3H/HeJ * CBA/J

integument

darkened coat color ( J:143333 )

• dark-like homozygotes heterozygous for yellow have much darker dorsal hair than mice heterozygous for both mutations, placing dark-like downstream of agouti transcription

pigmentation

darkened coat color ( J:143333 )

• dark-like homozygotes heterozygous for yellow have much darker dorsal hair than mice heterozygous for both mutations, placing dark-like downstream of agouti transcription

growth/size/body

obese ( J:143333 )

• mice heterozygous for yellow are obese and longer than normal to the same degree regardless of being wild-type or homozygous for dark-like

Genotype
MGI:5605683

cx9

• Allelic Composition: Pepd^dal/Pepd^dal; Tg(ACTB-Atrnl1)B4Tmg/0
• Genetic Background: involves: C57BL/6 * CBA/J * DBA/J

integument

darkened coat color ( J:143333 )

• transgenic overexpression of attractin does not alter the darkened dorsal coat color of dark-like homozygotes

pigmentation

darkened coat color ( J:143333 )

• transgenic overexpression of attractin does not alter the darkened dorsal coat color of dark-like homozygotes

endocrine/exocrine glands

abnormal testis morphology ( J:143333 )

♂ • transgenic overexpression of attractin does not prevent the formation of testicular vacuoles, which are found by 5 months of age

reproductive system

abnormal testis morphology ( J:143333 )

♂ • transgenic overexpression of attractin does not prevent the formation of testicular vacuoles, which are found by 5 months of age

Genotype
MGI:5605682

cx10

• Allelic Composition: Mc1r^e/Mc1r^e; Pepd^dal/Pepd^dal
• Genetic Background: involves: C57BL/6J * CBA/J

integument

yellow coat color ( J:143333 )

• double homozygotes have a clear yellow coat color indistingishable from e homozygotes

pigmentation

yellow coat color ( J:143333 )

• double homozygotes have a clear yellow coat color indistingishable from e homozygotes

growth/size/body

decreased body size ( J:143333 )

• some, but not all, are smaller than normal at wean age