Phenotypes associated with this allele

• Allele Symbol: Acvr2a^tm1Hsch
• Allele Name: targeted mutation 1,Heinrich Schrewe
• Allele ID: MGI:2179547
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch	involves: 129S1/Sv * C57BL/6J	MGI:3696941
cn2	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl Tg(Tyr-cre)1Lru/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * DBA/2	MGI:6258685
cn3	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl Tg(Tyr-cre)1Lru/Y	involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * DBA/2	MGI:6258677
cn4	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl Tg(KRT14-cre)1Ipc/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:6258667
cn5	Acvr2a^tm1Hsch/Acvr2a^+ Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl Tg(KRT14-cre)1Ipc/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:6258674
cx6	Acvr2a^tm1Hsch/Acvr2a^+ Acvr2b^tm1Spo/Acvr2b^tm1Spo	involves: 129S1/Sv * 129S4/SvJae	MGI:3697596
cx7	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Acvr2b^tm1Enl/Acvr2b^tm1Enl	involves: 129S1/Sv * 129S4/SvJae * C57BL/6J	MGI:3696942
cx8	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Acvr2b^tm1Enl/Acvr2b^+	involves: 129S1/Sv * 129S4/SvJae * C57BL/6J	MGI:3696943
cx9	Acvr2a^tm1Hsch/Acvr2a^+ Acvr2b^tm1Enl/Acvr2b^tm1Enl	involves: 129S1/Sv * 129S4/SvJae * C57BL/6J	MGI:3696945
cx10	Acvr2a^tm1Hsch/Acvr2a^+ Acvr2b^tm1.1Spo/Acvr2b^tm1.1Spo	involves: 129S1/Sv * 129S4/SvJae * FVB/N	MGI:3697597
cx11	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Acvr2b^tm1.1Spo/Acvr2b^tm1.1Spo	involves: 129S1/Sv * 129S4/SvJae * FVB/N	MGI:3697598
cx12	Acvr2a^tm1Hsch/Acvr2a^tm1Hsch Nodal^tm1Rob/Nodal^+	involves: 129S/SvEv * 129S1/Sv * C57BL/6J	MGI:3696946

Genotype
MGI:3696941

hm1

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:57262 )

• about 15% show mid-gestation lethality

embryo

abnormal gastrulation ( J:57262 )

• about 15% show severe gastrulation defects

craniofacial

mandible hypoplasia ( J:57262 )

• low frequency of mandible hypoplasia

endocrine/exocrine glands

abnormal testis development ( J:57262 )

♂ • delay in maturation of the testes

reproductive system

abnormal testis development ( J:57262 )

♂ • delay in maturation of the testes

reduced female fertility ( J:57262 )

♀ • partial sterility of females

skeleton

mandible hypoplasia ( J:57262 )

• low frequency of mandible hypoplasia

vision/eye

cyclopia ( J:57262 )

• low frequency of mild cyclopia

Genotype
MGI:6258685

cn2

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl; Tg(Tyr-cre)1Lru/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * DBA/2

pigmentation

mosaic coat color ( J:189569 )

♀ • female pups develop gray hair mosaically, consistent with the mosaic inactivation of the transgene-carrying X chromosome

integument

mosaic coat color ( J:189569 )

♀ • female pups develop gray hair mosaically, consistent with the mosaic inactivation of the transgene-carrying X chromosome

Genotype
MGI:6258677

cn3

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl; Tg(Tyr-cre)1Lru/Y
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * DBA/2

pigmentation

abnormal coat/hair pigmentation ( J:189569 )

♂ • male pups show a dramatic hypopigmentation of the hair coat

abnormal hair follicle melanin granule morphology ( J:189569 )

♂ • gray-haired skin shows normal melanocyte distribution but substantially less melanin in the hair follicles than control skin

♂ • a reduction in melanin is noted in the hair bulb, where melanocytes form a conical cluster

reduced hair shaft melanin granule number ( J:189569 )

♂ • a reduction in melanin is noted in the hair shaft

diluted coat color ( J:189569 )

♂ • male pups develop uniformly gray coats; gray hair develops during the first period of hair production

small melanosome ( J:189569 )

♂ • melanocytes of gray-haired skin produce numerous, dakly-pigmented miniaturized melanosomes, indicating impaired melanosome growth with no significant reduction in melanosome number or pigment-making ability

♂ • failure of melanosomes to grow leads to less production/accumulation of melanin per melanosome

♂ • miniaturized melanosomes are still transferred to epithelial cells of the hair shaft but hair shafts receive less pigment in total, resulting in hypopigmentation and gray color

integument

abnormal coat/hair pigmentation ( J:189569 )

♂ • male pups show a dramatic hypopigmentation of the hair coat

abnormal hair follicle melanin granule morphology ( J:189569 )

♂ • gray-haired skin shows normal melanocyte distribution but substantially less melanin in the hair follicles than control skin

♂ • a reduction in melanin is noted in the hair bulb, where melanocytes form a conical cluster

reduced hair shaft melanin granule number ( J:189569 )

♂ • a reduction in melanin is noted in the hair shaft

diluted coat color ( J:189569 )

♂ • male pups develop uniformly gray coats; gray hair develops during the first period of hair production

Genotype
MGI:6258667

cn4

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl; Tg(KRT14-cre)1Ipc/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * SJL

mortality/aging

perinatal lethality, complete penetrance ( J:189569 )

• mice die around the time of birth

• however, no skin a barrier defect is observed

vision/eye

eyelids open at birth ( J:189569 )

integument

abnormal hair growth ( J:189569 )

• mice exhibit defects in hair development and retention; newborn skin fails to generate coat hair fibers or vibrissae

absent hair follicle bulb ( J:189569 )

• coat follicles typically lack hair bulbs

abnormal hair follicle development ( J:189569 )

• newborns show impaired hair follicle morphogenesis

• however, the epidermis is intact

underdeveloped hair follicles ( J:189569 )

• coat and vibrissa hair follicles appear to be slowed or arrested in their development

abnormal vibrissa follicle morphology ( J:189569 )

• vibrissa follicles possess hair bulbs but are short, showing less downgrowth into the dermis, and generally lack terminally differentiating structures (e.g. the inner root sheath and hair shaft) and terminal differentiation markers (e.g. trichohyalin)

absent vibrissae ( J:189569 )

• vibrissa follicles generally lack the hair shaft

Genotype
MGI:6258674

cn5

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a⁺; Bmpr2^tm1.1Enl/Bmpr2^tm1.1Enl; Tg(KRT14-cre)1Ipc/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6 * SJL

integument

abnormal coat/ hair morphology ( J:189569 )

• at P20, awl, auchene, and zigzag hairs are markedly shorter than normal (consistent with premature entry into catagen), while the normally straightest hair types - guard and awl - are curved

• at P20, awl and auchene hairs lack multiple columns of medullary cells and have instead a single column; as such, awl/auchene hairs possess zigzag-like medullas and widths equivalent to normal zigzag fibers, making them markedly thinner than normal awl/auchene hairs

abnormal auchene hair morphology ( J:189569 )

• at P20, auchene hairs are markedly shorter and thinner than normal

abnormal awl hair morphology ( J:189569 )

• at P20, awl hairs are markedly shorter and thinner than normal

abnormal hair growth ( J:189569 )

• coats undergo repeated cycles of hair loss and regrowth throughout life

alopecia ( J:189569 )

• mice exhibit cyclic alopecia

• starting at ~P14, mice undergo total, progressive loss of coat hair in a face-to-tail sequence such that mice are completely bald by ~3 weeks of age; shortly after total coat hair loss, a new hair coat forms in full once more, and this coat is quickly lost again after reaching its maximum length

premature hair regrowth ( J:189569 )

• hair follicles enter anagen precociously, leading to a greater number of hair cycles

striated fur ( J:189569 )

• adult mice display hair growth and loss simultaneously, resulting in the appearance of stripes of coat hair and bald skin

abnormal hair shaft morphology ( J:189569 )

• hair shafts fail to develop hair clubs and exhibit ends of variable length that are tapered, thin, and wavy

• comb-collected hair fibers show the same tapered ends as those gathered with a forceps

increased curvature of awl hairs ( J:189569 )

• at P20

abnormal hair shaft melanin granule distribution ( J:189569 )

• amorphous clumping of the medullary pigment is observed in all hair types

increased curvature of guard hairs ( J:189569 )

• at P20

absent hair club ( J:189569 )

• failure to develop hair clubs appears to be the primary cause of total hair loss

abnormal hair medulla ( J:189569 )

• the hair medulla shows structural disorganization and differentiation defects

• at P11, the hair medulla shows many ectopic BrdU-labeled (proliferating) cells which are normally absent from the differentiating hair shaft

abnormal hair medullary septa cells ( J:189569 )

• medullary cells appear disorganized and fail to form well-defined ladders of pigment bands in all hair types; amorphous clumping of medullary pigment is observed

• medullary trichohyalin is greatly reduced, suggesting that medullary cells fail to differentiate properly

• awl and auchene hair follicles fail to produce multiple columns of medullary cells, generating a single column instead; as such, awl/auchene hairs possess zigzag-like medullas

thin hair shaft ( J:189569 )

• following birth, a dense coat is formed but a subset of hair shafts are thinner than those in control mice

abnormal zigzag hair morphology ( J:189569 )

• at P20, zigzag hairs are markedly shorter than normal

long nails ( J:189569 )

• mice exhibit excessive nail growth after 2 months of age

abnormal hair follicle outer root sheath morphology ( J:189569 )

• during catagen, mice show an increase in proliferating cells in the permanent" or superficial segment of the ORS that survives catagen

abnormal hair cycle ( J:189569 )

• mice exhibit a shift in the anagen/catagen transition, leading to the premature end of anagen and early induction of catagen

early exit from anagen phase ( J:189569 )

• mice exhibit shortened anagens; similar to the first period of hair production, the second period is also shorter, averaging 10.7 days versus 12.4 days in control mice

abnormal hair cycle catagen phase ( J:189569 )

• mice exhibit premature yet prolonged catagens

• catagen starts early with narrowing, amelanotic hair bulbs observed as early as P15, a time when controls continue to grow hair

• by P16-17, all hair follicles have entered catagen but progression through this phase of the hair cycle is slow

• however, no differences in apoptosis are observed during catagen

early exit from telogen phase ( J:189569 )

• coat follicles always exhibit shortened telogens, as new hair is produced soon after the preceding hair fibers are lost

• at P50, the coat follicles have left the second telogen and uniformly re-entered anagen, whereas those of controls mice are still in the second telogen

abnormal hair follicle regression ( J:189569 )

• hair follicles are still regressing at P20, as shown by the presence of extended epithelial strands (involuting remnants of the outer root sheath and hair bulb)

• slowly regressing epithelial strands often appear abnormally curled; concomitant with impaired follicular involution, hair shafts disappear from the skin

increased hair follicle cell proliferation ( J:189569 )

• at P18 (during catagen), BrdU-labeled cells are increased in the superficial segments of the hair follicles

thick epidermis ( J:189569 )

• at the onset of anagen, mice exhibit a thicker epidermis consistent with an increased number of BrdU-labeled cells in the epidermis

pigmentation

abnormal hair shaft melanin granule distribution ( J:189569 )

• amorphous clumping of the medullary pigment is observed in all hair types

Genotype
MGI:3697596

cx6

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a⁺; Acvr2b^tm1Spo/Acvr2b^tm1Spo
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae

skeleton

lumbar vertebral transformation ( J:114533 )

• 100% penetrance of vertebral transformation of the 21st vertebra into the 14th thoracic vertebra

embryo

abnormal left-right axis patterning ( J:114533 )

• 12 of 13 show effects associated with left-right asymmetry such as right pulmonary isomerism and transposition of great arteries

cardiovascular system

transposition of great arteries ( J:114533 )

respiratory system

right pulmonary isomerism ( J:114533 )

growth/size/body

right pulmonary isomerism ( J:114533 )

Genotype
MGI:3696942

cx7

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Acvr2b^tm1Enl/Acvr2b^tm1Enl
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6J

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:57262 )

• die before or during gastrulation and are resorbed by E8.5

embryo

increased embryonic epiblast cell apoptosis ( J:57262 )

• cell death is seen in the epiblast of some embryos

failure to gastrulate ( J:57262 )

embryonic growth arrest ( J:57262 )

• embryos are growth arrested at the early egg cylinder stage

absent mesoderm ( J:57262 )

• do not form mesoderm

embryonic-extraembryonic boundary constriction ( J:57262 )

• exhibit a constriction at the embryonic and extraembryonic junction and the separation of the visceral endoderm and the epiblast

cellular

increased embryonic epiblast cell apoptosis ( J:57262 )

• cell death is seen in the epiblast of some embryos

Genotype
MGI:3696943

cx8

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Acvr2b^tm1Enl/Acvr2b⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6J

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:57262 )

• die before or during gastrulation; by E9.5, embryos are partially or completely degenerated

embryo

abnormal gastrulation ( J:57262 )

• gastrulation is initiated but severely impaired subsequently

• severe gastrulation defects ranging from the lack of discernible embryonic axes to the formation or relatively normal axial and paraxial structures

abnormal mesoderm development ( J:57262 )

• formation of the embryonic mesoderm is severely impaired

abnormal rostral-caudal axis patterning ( J:57262 )

• exhibit defects in anterior patterning as indicated by marker expression

• the few embryos that are able to undergo relatively normal gastrulation, exhibit abnormal anterior neural development

embryonic growth arrest ( J:57262 )

absent head fold ( J:57262 )

• almost all embryos with gastrulation defects do not form the head-fold structure

embryonic-extraembryonic boundary constriction ( J:57262 )

• often show a constriction at the embryonic and extraembryonic junction, leading to the protrusion of embryos outside the yolk sac at E8.5

abnormal primitive streak elongation ( J:57262 )

• primitive streak elongation is disrupted

absent allantois ( J:57262 )

• absent in most mutants

absent amnion ( J:57262 )

• absent in most mutants

cardiovascular system

absent heart tube ( J:57262 )

• almost all embryos with gastrulation defects do not form a primitive heart

Genotype
MGI:3696945

cx9

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a⁺; Acvr2b^tm1Enl/Acvr2b^tm1Enl
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6J

mortality/aging

perinatal lethality, complete penetrance ( J:57262 )

• die late in development or shortly after birth

Genotype
MGI:3697597

cx10

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a⁺; Acvr2b^tm1.1Spo/Acvr2b^tm1.1Spo
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * FVB/N

skeleton

lumbar vertebral transformation ( J:114533 )

• 6 of 16 exhibit transformation of the 21st vertebra into the 14th thoracic vertebra

embryo

abnormal left-right axis patterning ( J:114533 )

• 12 of 13 show effects associated with left-right asymmetry such as right pulmonary isomerism and transposition of great arteries

cardiovascular system

transposition of great arteries ( J:114533 )

respiratory system

right pulmonary isomerism ( J:114533 )

growth/size/body

right pulmonary isomerism ( J:114533 )

Genotype
MGI:3697598

cx11

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Acvr2b^tm1.1Spo/Acvr2b^tm1.1Spo
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * FVB/N

mortality/aging

embryonic lethality between somite formation and embryo turning ( J:114533 )

embryo

embryonic growth arrest ( J:114533 )

• development is arrested at the gastrulation stage (E8.5)

abnormal embryonic tissue morphology ( J:114533 )

• the embryonic tissues grow outside of the yolk sac

embryonic-extraembryonic boundary constriction ( J:114533 )

• exhibit constrictions at the junction between the extraembryonic and embryonic regions at E7.5

Genotype
MGI:3696946

cx12

• Allelic Composition: Acvr2a^tm1Hsch/Acvr2a^tm1Hsch; Nodal^tm1Rob/Nodal⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6J

mortality/aging

embryonic lethality, complete penetrance ( J:57262 )

• embryonic lethality although time not specified

embryo

abnormal gastrulation ( J:57262 )

• over 60% show gastrulation defects

nervous system

decreased forebrain size ( J:57262 )

• 4 of 13 embryos that developed beyond gastrulation have a reduced forebrain

vision/eye

cyclopia ( J:57262 )

• 6 of 8 newborns display cyclopia

growth/size/body

abnormal head morphology ( J:57262 )

• 6 of 8 newborns show truncation of rostral head structures