Phenotypes associated with this allele

• Allele Symbol: Yy1^tm2.1Yshi
• Allele Name: targeted mutation 2.1, Yang Shi
• Allele ID: MGI:3624790
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi	involves: 129S4/SvJae	MGI:3625998
cn2	Dicer1^tm1Bdh/Dicer1^+ Yy1^tm2.1Yshi/Yy1^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129 * 129S4/SvJae * C57BL/6	MGI:5902326
cn3	Yy1^tm1Yshi/Yy1^tm2.1Yshi Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:6446753
cn4	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Tg(Dct-lacZ)A12Jkn/0 Tg(Tyr-cre)1Lru/Y	involves: 129S4/SvJae * C57BL/6 * CBA * DBA/2	MGI:6226060
cn5	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Tg(Tyr-cre)1Lru/Y	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:6226058
cn6	Tg(Zp3-cre)93Knw/0 Yy1^tm1Yshi/Yy1^tm2.1Yshi	involves: 129S4/SvJae * C57BL/6J	MGI:7280653
cn7	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * C57BL/6J	MGI:5902325
cn8	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S4/SvJae * C57BL/6J	MGI:5902322

Genotype
MGI:3625998

hm1

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi
• Genetic Background: involves: 129S4/SvJae

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

normal phenotype

no abnormal phenotype detected ( J:108369 )

• all survive and are similar in size to wild-type littermates

Genotype
MGI:5902326

cn2

• Allelic Composition: Dicer1^tm1Bdh/Dicer1⁺; Yy1^tm2.1Yshi/Yy1⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6

respiratory system

respiratory system phenotype ( J:239777 )

N • embryos do not present lung defects

Genotype
MGI:6446753

cn3

• Allelic Composition: Yy1^tm1Yshi/Yy1^tm2.1Yshi; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

embryo

abnormal gastrulation ( J:186556 )

• at E7.0, Nodal is ectopically expressed throughout the posterior half of the epiblast, instead of being confined to the anterior streak as in control embryos; by E7.5, Nodal is expressed throughout the posterior epiblast and streak derivates instead of being confined to the node as in control embryos

• at E7.0, Foxa2 is properly localized to the anterior visceral endoderm (AVE) but is aberrantly expressed throughout distally located streak derived cells; by E7.5, Foxa2 is inappropriately expressed in a large swath of distally located streak derived cells

abnormal gastrulation movements ( J:186556 )

• embryonic to extraembryonic signaling is impaired, resulting in aberrant morphogenetic movements during gastrulation

abnormal endoderm development ( J:186556 )

• definitive endoderm (DE) is specified but fails to properly integrate into the outer layer; Hex-positive DE cells fail to intercalate into the visceral endoderm (VE)

abnormal mesoderm development ( J:186556 )

• although anterior neuroectoderm is specified, mesoderm production is severely restricted

• analysis of nascent mesoderm markers shows that Lefty2 and Fgf4 are completely absent at E7.5 while Snail and Fgf8 expression is markedly reduced with weak areas of expression confined to the distal-most mesoderm at E7.0

• pharmacological inhibition of Nodal signaling with SB505124 partially restores mesoderm production: in culture, SB505124-treated embryos show increased mesodermal-like streak derivatives, a slight increase in T expression, a marked increase in mesodermal marker transcripts (Tbx6, Twist1 and Snail), a reduction of Nodal, Cer1, Eomes and Foxa2, but no effect on the loss of Lefty2 or Fgf4, suggesting that both Nodal-dependent and Nodal-independent events contribute to the gastrulation defects

abnormal rostral-caudal axis patterning ( J:186556 )

• although expression of both Cer1 and Hex is properly localized to the anterior visceral endoderm (AVE) at E7.0, expression of both genes is significantly reduced, suggesting impaired embryonic (epiblast) to extraembryonic (AVE) signaling

• at E7.0, the Otx2 expression domain is reduced and fails to become anteriorly restricted; by E7.5 Otx2 is confined to a small population of distal epiblast cells

• however, Oct4 and Sox2 expression is normal at E7.0 and E7.5, indicating that neural specification is initiated

decreased embryo size ( J:186556 )

• embryos are smaller than controls at E6.5 and E7.0

absent head fold ( J:186556 )

• no head folds are present at E7.5

absent notochord ( J:186556 )

• no morphological notochord is present at E7.5

absent primitive node ( J:186556 )

• no morphological embryonic node is present at E7.5

abnormal primitive streak formation ( J:186556 )

• although embryos initiate gastrulation, both primitive streak (PS) formation and ingression through the streak is severely impaired

• at E7.5, a PS is present but shows a distinct accumulation of cells proximal to the streak, suggesting defects in epithelial to mesenchymal transition (EMT)

• PS derivatives fail to repress E-cadherin (CDH1) and migrate properly, unlike in wild-type embryos

• PS formation is compromised, as indicated by reduced brachyury (T) expression, loss of the mesoderm markers Lefty2, Snail and Fgf8, and excess extraembryonic and embryonic Bmp4 and Eomes

abnormal primitive streak elongation ( J:186556 )

• at E7.0, the expression domain of brachyury (T) is decreased relative to controls; by E7.5, T expression has failed to extend distally, consistent with a drastic reduction in overall streak size

abnormal extraembryonic tissue morphology ( J:186556 )

• E7.5 embryos exhibit an abnormal extraembryonic region

abnormal extraembryonic ectoderm morphology ( J:186556 )

• Eomes and Bmp4 are overexpressed in the distal extraembryonic ectoderm at E7.0 and E7.5, respectively, instead of being downregulated as in control embryos

abnormal visceral endoderm morphology ( J:186556 )

• at E7.5, a thickened HNF4A-positive visceral endoderm (VE) surrounds both the embryonic and extraembryonic tissues of the conceptus, unlike in control embryos where VE surrounds only the extraembryonic tissues, indicating an absence of the DE-mediated dispersal of VE

growth/size/body

decreased embryo size ( J:186556 )

• embryos are smaller than controls at E6.5 and E7.0

Genotype
MGI:6226060

cn4

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi; Tg(Dct-lacZ)A12Jkn/0; Tg(Tyr-cre)1Lru/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA * DBA/2

Absence of melanocytes or pigment in hair follicles of Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Tg(Tyr-cre)1Lru/Y Tg(Dct-lacZ)A12Jkn/0 mice at the anagen phase of the second hair cycle

pigmentation

abnormal hair follicle melanocyte morphology ( J:185128 )

♂ • mice show absence of differentiated melanocytes in hair follicles at the anagen phase of the second hair cycle (P38)

absent hair follicle melanin granules ( J:185128 )

♂ • mice show absence of pigment in hair follicles at the anagen phase of the second hair cycle (P38)

decreased melanocyte number ( J:185128 )

♂ • absence of differentiated melanocytes in hair follicles at P38

integument

abnormal hair follicle melanocyte morphology ( J:185128 )

♂ • mice show absence of differentiated melanocytes in hair follicles at the anagen phase of the second hair cycle (P38)

absent hair follicle melanin granules ( J:185128 )

♂ • mice show absence of pigment in hair follicles at the anagen phase of the second hair cycle (P38)

embryo

abnormal melanoblast morphology ( J:185128 )

♂ • absence of Dct-LacZ+ melanocyte stem cells (melanoblasts) in hair follicles at P38

nervous system

abnormal melanoblast morphology ( J:185128 )

♂ • absence of Dct-LacZ+ melanocyte stem cells (melanoblasts) in hair follicles at P38

Genotype
MGI:6226058

cn5

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi; Tg(Tyr-cre)1Lru/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

Skin and hair pigmentation phenotype of Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Tg(Tyr-cre)1Lru/Y mice

pigmentation

abnormal coat/hair pigmentation ( J:185128 )

♂ • mice exhibit premature gray hair after the first hair cycle

abnormal dorsoventral coat patterning ( J:185128 )

♂ • during the first hair cycle (P0-P28), P10 ventral hairs are essentially devoid of pigment, whereas hairs from dorsal skin are much less pigmented than those in control mice; however, white dorsal fur is observed by P45

abnormal hair follicle melanocyte morphology ( J:185128 )

♂ • in the second hair cycle anagen phase (P28-P42), new dorsal hair follicles completely lack DCT+ melanocytes, corresponding to subsequent white dorsal fur seen at P45

abnormal hair follicle melanin granule morphology ( J:185128 )

♂ • at P4, dorsal skin shows small amounts of residual hair follicle melanin; residual dorsal melanocytes (DCT+) continue to express YY1, indicating incomplete Cre-mediated deletion

absent hair follicle melanin granules ( J:185128 )

♂ • in the second hair cycle anagen phase (P28-P42), new dorsal hair follicles completely lack melanin pigment

decreased skin pigmentation ( J:185128 )

♂ • at P4, mice show profoundly lighter skin pigmentation relative to control mice

decreased melanocyte number ( J:185128 )

♂ • mice exhibit complete loss of hair follicle melanocytes after the first hair cycle

integument

abnormal coat/hair pigmentation ( J:185128 )

♂ • mice exhibit premature gray hair after the first hair cycle

abnormal dorsoventral coat patterning ( J:185128 )

♂ • during the first hair cycle (P0-P28), P10 ventral hairs are essentially devoid of pigment, whereas hairs from dorsal skin are much less pigmented than those in control mice; however, white dorsal fur is observed by P45

abnormal hair follicle melanocyte morphology ( J:185128 )

♂ • in the second hair cycle anagen phase (P28-P42), new dorsal hair follicles completely lack DCT+ melanocytes, corresponding to subsequent white dorsal fur seen at P45

abnormal hair follicle melanin granule morphology ( J:185128 )

♂ • at P4, dorsal skin shows small amounts of residual hair follicle melanin; residual dorsal melanocytes (DCT+) continue to express YY1, indicating incomplete Cre-mediated deletion

absent hair follicle melanin granules ( J:185128 )

♂ • in the second hair cycle anagen phase (P28-P42), new dorsal hair follicles completely lack melanin pigment

decreased skin pigmentation ( J:185128 )

♂ • at P4, mice show profoundly lighter skin pigmentation relative to control mice

Genotype
MGI:7280653

cn6

• Allelic Composition: Tg(Zp3-cre)93Knw/0; Yy1^tm1Yshi/Yy1^tm2.1Yshi
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

reproductive system

abnormal oocyte morphology ( J:170240 )

♀ • oocytes rarely grow larger than 50 um in diameter, indicating arrested oocyte growth

♀ • oocyte-specific expression of Gdf9 and Bmp15 is nearly undetectable

♀ • oocytes exhibit altered levels of several oocyte-specific factors, including Pou5f1, Figla, Lhx8, Oosp1, and Sohlh2

oocyte degeneration ( J:170240 )

♀ • secondary follicles often contain a degenerating oocyte

absent mature ovarian follicles ( J:170240 )

♀ • no mature follicles are observed

increased primary ovarian follicle number ( J:170240 )

♀ • percent of follicles in the primary stage is significantly higher than in controls (83% versus 20%)

absent tertiary ovarian follicles ( J:170240 )

♀ • no multilayered, antral follicles or Graafian follicles are observed

impaired ovarian folliculogenesis ( J:170240 )

♀ • ovarian follicle maturation is halted; no post-secondary follicles are observed

♀ • however, no differences are observed in the number of primordial follicles

abnormal secondary ovarian follicle morphology ( J:170240 )

♀ • some secondary follicles exhibit an irregular/incomplete second layer of granulosa cells and often contain a degenerating oocyte

decreased secondary ovarian follicle number ( J:170240 )

♀ • percent of follicles in the secondary stage is significantly lower than in controls (17% versus 45%)

small ovary ( J:170240 )

♀ • adult females show a ~30% reduction in ovary size relative to control females

abnormal ovary physiology ( J:170240 )

♀ • in whole ovaries, mRNA levels of Gdf9 and Bmp15 are nearly undetectable, whereas mRNA levels of Bmp6, Kit, and Kitl are significantly increased relative to control ovaries

absent estrous cycle ( J:170240 )

♀ • although vaginal cytology indicates estrus stage changes, no regular cycle or periodicity is observed during a 3-wk test period indicating failure of estrus cycling

female infertility ( J:170240 )

♀ • when placed individually with wild-type males, 6-wk-old females never appeared pregnant or produced offspring

homeostasis/metabolism

abnormal circulating hormone level ( J:170240 )

♀ • serum inhibin-A levels are decreased or undetectable in all females examined, regardless of staging by vaginal cytology

increased circulating follicle stimulating hormone level ( J:170240 )

♀ • serum FSH levels are dramatically increased in females, regardless of staging by vaginal cytology

behavior/neurological

decreased copulatory plug deposition ( J:170240 )

• vaginal plugs are infrequently detected during a 5-mo breeding trial

cellular

abnormal oocyte morphology ( J:170240 )

♀ • oocytes rarely grow larger than 50 um in diameter, indicating arrested oocyte growth

♀ • oocyte-specific expression of Gdf9 and Bmp15 is nearly undetectable

♀ • oocytes exhibit altered levels of several oocyte-specific factors, including Pou5f1, Figla, Lhx8, Oosp1, and Sohlh2

oocyte degeneration ( J:170240 )

♀ • secondary follicles often contain a degenerating oocyte

endocrine/exocrine glands

absent mature ovarian follicles ( J:170240 )

♀ • no mature follicles are observed

increased primary ovarian follicle number ( J:170240 )

♀ • percent of follicles in the primary stage is significantly higher than in controls (83% versus 20%)

absent tertiary ovarian follicles ( J:170240 )

♀ • no multilayered, antral follicles or Graafian follicles are observed

impaired ovarian folliculogenesis ( J:170240 )

♀ • ovarian follicle maturation is halted; no post-secondary follicles are observed

♀ • however, no differences are observed in the number of primordial follicles

abnormal secondary ovarian follicle morphology ( J:170240 )

♀ • some secondary follicles exhibit an irregular/incomplete second layer of granulosa cells and often contain a degenerating oocyte

decreased secondary ovarian follicle number ( J:170240 )

♀ • percent of follicles in the secondary stage is significantly lower than in controls (17% versus 45%)

small ovary ( J:170240 )

♀ • adult females show a ~30% reduction in ovary size relative to control females

abnormal ovary physiology ( J:170240 )

♀ • in whole ovaries, mRNA levels of Gdf9 and Bmp15 are nearly undetectable, whereas mRNA levels of Bmp6, Kit, and Kitl are significantly increased relative to control ovaries

Genotype
MGI:5902325

cn7

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

lethality at weaning, complete penetrance ( J:239777 )

• a small percentage of mutants survive up to weaning age

neonatal lethality, incomplete penetrance ( J:239777 )

• most mutants die at birth but some survive up to weaning age

neoplasm

increased blastoma incidence ( J:239777 )

• mice surviving to weaning exhibit characteristics of an evolving type I pleuropulmonary blastoma-like phenotype

respiratory system

lung cyst ( J:239777 )

• embryos exhibit cysts in the proximal region of lung lobes

• Type I and II pneumocytes, but not club and ciliated cells, are present along the cystic epithelium

• P21 lungs show multiocular cysts and variable septal thickness, small mesenchymal cells within the cyst walls, high proliferation levels of mesenchymal cells within the cystic wall

abnormal respiratory epithelium physiology ( J:239777 )

• increase in proliferation in E18.5 lungs

growth/size/body

lung cyst ( J:239777 )

• embryos exhibit cysts in the proximal region of lung lobes

• Type I and II pneumocytes, but not club and ciliated cells, are present along the cystic epithelium

• P21 lungs show multiocular cysts and variable septal thickness, small mesenchymal cells within the cyst walls, high proliferation levels of mesenchymal cells within the cystic wall

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pleuropulmonary blastoma		DOID:4769		J:239777

Genotype
MGI:5902322

cn8

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

neonatal lethality, complete penetrance ( J:239777 )

• all newborns die at birth from respiratory failure

growth/size/body

lung cyst ( J:239777 )

• E18.5 lungs show the presence of dilated fluid-filled sacs

• proliferation assays in lungs from E18.5 fetuses show an increase in cell proliferation in cystic walls

• neither secretory club (Clara) cells or ciliated cells are seen in cyst epithelium at E18.5 and cysts are lined by Type II and Type I pneumocytes

• a microvascular network is present in the parenchyma forming the cyst walls

left pulmonary isomerism ( J:239777 )

• E12.5 lungs show two hypoplastic lobes instead of the expected asymmetric pattern of 4 right lobes and 1 left lobe

respiratory system

increased lung apoptosis ( J:239777 )

• apoptosis is increased in lung mesenchyme at E14.5

• E12.5 embryos cultured in vitro show increased apoptosis in the lung

• the addition of recombinant mouse SHH into the media rescues the increased apoptosis

abnormal lung morphology ( J:239777 )

• E18.5 lungs exhibit a disorganized architecture

lung cyst ( J:239777 )

• E18.5 lungs show the presence of dilated fluid-filled sacs

• proliferation assays in lungs from E18.5 fetuses show an increase in cell proliferation in cystic walls

• neither secretory club (Clara) cells or ciliated cells are seen in cyst epithelium at E18.5 and cysts are lined by Type II and Type I pneumocytes

• a microvascular network is present in the parenchyma forming the cyst walls

left pulmonary isomerism ( J:239777 )

• E12.5 lungs show two hypoplastic lobes instead of the expected asymmetric pattern of 4 right lobes and 1 left lobe

abnormal lung development ( J:239777 )

• marker analysis indicates altered patterning and cell differentiation in the lung

abnormal branching involved in lung morphogenesis ( J:239777 )

• branching morphogenesis in the lung is inhibited, however, distal epithelial cell differentiation is maintained

• E12.5 embryos cultured in vitro fail with branching of lung

• the addition of recombinant mouse SHH into the media does not rescue the branching defect

abnormal lung-associated mesenchyme development ( J:239777 )

• impairment of peribronchial smooth muscle differentiation as indicated by a lack of markers of airway smooth muscle differentiation around cysts

abnormal lung epithelium morphology ( J:239777 )

• lung epithelium exhibits an abnormal stratified structure at E12.5

decreased club cell number ( J:239777 )

• club (Clara) cells are scarce in the proximal airways

abnormal airway basal cell morphology ( J:239777 )

• basal cells are distributed irregularly along the proximal airways of embryos, although the number of basal cells is not altered

decreased respiratory mucosa goblet cell number ( J:239777 )

• goblet cells are scarce in the proximal airways

abnormal trachea morphology ( J:239777 )

• trachea is thinner with disorganized cartilage rings

• trachea is longer

abnormal tracheal ciliated epithelium morphology ( J:239777 )

• ciliated cells are scarce in the airways

abnormal tracheal cartilage morphology ( J:239777 )

• trachea shows abnormal formation of cartilage rings

trachea stenosis ( J:239777 )

respiratory failure ( J:239777 )

abnormal respiratory epithelium physiology ( J:239777 )

• reduction in lung epithelium proliferation at E12.5

cellular

increased lung apoptosis ( J:239777 )

• apoptosis is increased in lung mesenchyme at E14.5

• E12.5 embryos cultured in vitro show increased apoptosis in the lung

• the addition of recombinant mouse SHH into the media rescues the increased apoptosis

impaired myofibroblast differentiation ( J:239777 )

• differentiation of airway myofibroblasts is impaired

skeleton

abnormal tracheal cartilage morphology ( J:239777 )

• trachea shows abnormal formation of cartilage rings