Phenotypes associated with this allele

• Allele Symbol: Ncoa6^tm1Hhs
• Allele Name: targeted mutation 1, Herbert H Samuels
• Allele ID: MGI:3046462
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ncoa6^tm1Hhs/Ncoa6^tm1Hhs	either: 129S6/SvEvTac or (involves: 129S6/SvEvTac * C57BL/6)	MGI:3046464
hm2	Ncoa6^tm1Hhs/Ncoa6^tm1Hhs	involves: 129S6/SvEvTac	MGI:3693879
ht3	Ncoa6^tm1Hhs/Ncoa6^+	129S6/SvEvTac-Ncoa6^tm1Hhs	MGI:3046465
ht4	Ncoa6^tm1Hhs/Ncoa6^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3046500

Genotype
MGI:3046464

hm1

• Allelic Composition: Ncoa6^tm1Hhs/Ncoa6^tm1Hhs
• Genetic Background: either: 129S6/SvEvTac or (involves: 129S6/SvEvTac * C57BL/6)

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

mortality/aging

embryonic lethality, complete penetrance ( J:91083 )

• homozygous embryos die between E8.5 and E12.5

cardiovascular system

abnormal vascular development ( J:91083 )

• decreased vascularization is seen

abnormal heart development ( J:91083 )

• developmental defects are seen in the heart

cellular

increased fibroblast apoptosis ( J:91083 )

• a higher percentage of late log phase immortalized MEFs from E12.5 embryos undergo apoptosis compared to wild-type MEFs

decreased fibroblast proliferation ( J:91083 )

• immortalized MEFs from E12.5 embryos double at about half the rate of wild-type MEFs

embryo

decreased embryo size ( J:91083 )

• homozygous embryos are about half the size of wild-type or heterozygous littermates

impaired placental function ( J:91083 )

• placental dysfunction is seen

growth/size/body

decreased embryo size ( J:91083 )

• homozygous embryos are about half the size of wild-type or heterozygous littermates

limbs/digits/tail

hindlimb oligodactyly ( J:91083 )

• some embryos are missing one of the digits on the hind limb or separation of the digits did not occur

liver/biliary system

abnormal liver development ( J:91083 )

• developmental defects are seen in the liver

nervous system

abnormal brain development ( J:91083 )

• developmental defects are seen in the brain

Genotype
MGI:3693879

hm2

• Allelic Composition: Ncoa6^tm1Hhs/Ncoa6^tm1Hhs
• Genetic Background: involves: 129S6/SvEvTac

cellular

abnormal cell physiology ( J:116064 )

• in culture, embryonic fibroblasts (MEFs) do not support retinoic acid receptor (RAR) transactivation

• histone H3-K4 trimethylation of RARbeta 2 is abolished in MEFs; H3 acetylation is also ablated in mutant cells

Genotype
MGI:3046465

ht3

• Allelic Composition: Ncoa6^tm1Hhs/Ncoa6⁺
• Genetic Background: 129S6/SvEvTac-Ncoa6^tm1Hhs

mortality/aging

neonatal lethality, incomplete penetrance ( J:91083 )

• Background Sensitivity: increased neonatal lethality is seen on a 129S6 background but not on a mixed 129S6 and C57BL/6 background

prenatal lethality, incomplete penetrance ( J:91083 )

• on a 129S6 background fewer than expected heterozygous embryos are born; however, embryonic lethality is not seen on a mixed 129S6 and C57BL/6 background

endocrine/exocrine glands

increased sebaceous gland number ( J:91083 )

• those heterozygotes that develop spontaneous wounds display an increase in the number of sebaceous glands

growth/size/body

decreased birth body size ( J:91083 )

• Background Sensitivity: neonates are small compared to wild-type, this occurs more frequently on a 129S6 background than on a mixed 129S6 and C57BL/6 background

decreased birth weight ( J:91083 )

• about 3% of the neonates on a 129S6 background weigh less than 70% of wild-type littermates and these often die before weaning

• the weight difference between heterozygous pups and wild-type littermates decreases between 1 - 2 months after birth

reproductive system

female infertility ( J:91083 )

♀ • about 20% of females on a 129S6 background are infertile

reduced female fertility ( J:91083 )

♀ • about 80% of females on a 129S6 background produce small litters when crossed to either wild-type or heterozygous males

♀ • Background Sensitivity: on a 129S6 background female fertility progressively decreases with repeated crossings

decreased litter size ( J:91083 )

• Background Sensitivity: heterozygous males and females produce small litters when on a 129S6 background but not when on a mixed 129S6/SvEv and C57BL/6 background

reduced male fertility ( J:91083 )

♂ • Background Sensitivity: on a 129S6 background males mated to wild-type females sire small litters; however, on a mixed 129S6 and C57BL/6 background fertility is not reduced

homeostasis/metabolism

delayed wound healing ( J:91083 )

• about 20% of heterozygotes develop spontaneous wounds around the head and neck and of these 25% show delayed wound healing

impaired wound healing ( J:91083 )

• about 20% of heterozygotes develop spontaneous wounds around the head and neck and for 75% of these 75% the wound does not heal

• no leading edge of keratinocyte migration is seen and in skin explant culture keratinocyte migratory capacity is significantly reduced

integument

increased sebaceous gland number ( J:91083 )

• those heterozygotes that develop spontaneous wounds display an increase in the number of sebaceous glands

decreased hair follicle number ( J:91083 )

• those heterozygotes that develop spontaneous wounds display a decrease in or total loss of hair follicles

thick epidermis ( J:91083 )

• those heterozygotes that develop spontaneous wounds display thickening of the epidermis around the wound

Genotype
MGI:3046500

ht4

• Allelic Composition: Ncoa6^tm1Hhs/Ncoa6⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

endocrine/exocrine glands

increased sebaceous gland number ( J:91083 )

• those heterozygotes that develop spontaneous wounds display an increase in the number of sebaceous glands around the wound site

growth/size/body

decreased birth body size ( J:91083 )

• Background Sensitivity: neonates are small compared to wild-type, this occurs more frequently on a 129S6 background than on a mixed 129S6/SvEv and C57BL/6 background

reproductive system

reproductive system phenotype ( J:91083 )

N • heterozygotes display normal fertility on a mixed 129S6 and C57BL/6 background

homeostasis/metabolism

delayed wound healing ( J:91083 )

• about 20% of heterozygotes develop spontaneous wounds around the head and neck and of these 25% show delayed wound healing

impaired wound healing ( J:91083 )

• about 20% of heterozygotes develop spontaneous wounds around the head and neck and for 75% of these 75% the wound does not heal

• no leading edge of keratinocyte migration is seen and in skin explant culture keratinocyte migratory capacity is significantly reduced

integument

increased sebaceous gland number ( J:91083 )

• those heterozygotes that develop spontaneous wounds display an increase in the number of sebaceous glands around the wound site

decreased hair follicle number ( J:91083 )

• those heterozygotes that develop spontaneous wounds display a decrease in or total loss of hair follicles around the wound site

thick epidermis ( J:91083 )

• those heterozygotes that develop spontaneous wounds display thickening of the epidermis around the wound