Phenotypes associated with this allele

• Allele Symbol: Fst^tm1Zuk
• Allele Name: targeted mutation 1, Martin M Matzuk
• Allele ID: MGI:1857467
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fst^tm1Zuk/Fst^tm1Zuk	B6.129S7-Fst^tm1Zuk	MGI:3589667
hm2	Fst^tm1Zuk/Fst^tm1Zuk	involves: 129S7/SvEvBrd	MGI:3042284
hm3	Fst^tm1Zuk/Fst^tm1Zuk	involves: 129S7/SvEvBrd * C57BL/6	MGI:3042286
ht4	Fst^tm1Zuk/Fst^+	B6.129S7-Fst^tm1Zuk	MGI:5319775
ht5	Fst^tm1Zuk/Fst^+	involves: 129S7/SvEvBrd	MGI:3814734
ht6	Fst^tm1Zuk/Fst^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3814735
cn7	Amhr2^tm3(cre)Bhr/Amhr2^+ Fst^tm1Zuk/Fst^tm2Zuk	involves: 129S/SvEv * C57BL/6J	MGI:3042275
cx8	Fst^tm1Zuk/Fst^+ Fstl3^tm1.1Sjl/Fstl3^tm1.1Sjl	B6.129-Fst^tm1Zuk Fstl3^tm1.1Sjl	MGI:5319774
cx9	Fst^tm1Zuk/Fst^+ Mstn^tm1Sjl/Mstn^+	B6.129-Mstn^tm1Sjl Fst^tm1Zuk	MGI:5319777
cx10	Fst^tm1Zuk/Fst^+ Mstn^tm1Sjl/Mstn^tm1Sjl	B6.129-Mstn^tm1Sjl Fst^tm1Zuk	MGI:5319776
cx11	Fst^tm1Zuk/Fst^tm1Zuk Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl	involves: 129S7/SvEvBrd * C57BL/6	MGI:5546336
cx12	Fst^tm1Zuk/Fst^+ Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl	involves: 129S7/SvEvBrd * C57BL/6	MGI:5546337
cx13	Fst^tm1Zuk/Fst^tm1Zuk Wfikkn1^tm1.1Sjl/Wfikkn1^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:5546338
cx14	Fst^tm1Zuk/Fst^tm1Zuk Gdf11^tm1Clf/Gdf11^tm1Clf	involves: 129X1/SvJ * C57BL/6J * CD-1	MGI:3589668

Genotype
MGI:3589667

hm1

• Allelic Composition: Fst^tm1Zuk/Fst^tm1Zuk
• Genetic Background: B6.129S7-Fst^tm1Zuk

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

nervous system

abnormal neuron differentiation ( J:81451 )

• homozygotes display decreased olfactory epithelium neurogenesis, as shown by significantly reduced neurogenin-1-expressing immediate neuronal precursors and Ncam1-expressing olfactory receptor neurons

abnormal olfactory sensory neuron morphology ( J:81451 )

• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

decreased neuronal precursor cell number ( J:81451 )

taste/olfaction

abnormal olfactory epithelium morphology ( J:81451 )

• homozygotes display a 38% decrease in thickness of the olfactory epithelium

abnormal olfactory sensory neuron morphology ( J:81451 )

• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

vision/eye

thin retina ganglion layer ( J:99244 )

• mutant retinas exhibit a 26% reduction in the number of cells in the ganglion cell layer and a marked decrease in thickness of the differentiated ganglion cell layer

• unlike the situation in olfactory epithelium, mutant retinas display normal overall thickness as well as normal progenitor cell proliferation

• in addition, mutant retinas show no obvious differences in amacrine cell or photoreceptor production relative to wild-type

respiratory system

abnormal olfactory epithelium morphology ( J:81451 )

• homozygotes display a 38% decrease in thickness of the olfactory epithelium

abnormal olfactory sensory neuron morphology ( J:81451 )

• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

craniofacial

abnormal olfactory epithelium morphology ( J:81451 )

• homozygotes display a 38% decrease in thickness of the olfactory epithelium

abnormal olfactory sensory neuron morphology ( J:81451 )

• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

cellular

abnormal neuron differentiation ( J:81451 )

• homozygotes display decreased olfactory epithelium neurogenesis, as shown by significantly reduced neurogenin-1-expressing immediate neuronal precursors and Ncam1-expressing olfactory receptor neurons

growth/size/body

abnormal olfactory epithelium morphology ( J:81451 )

• homozygotes display a 38% decrease in thickness of the olfactory epithelium

abnormal olfactory sensory neuron morphology ( J:81451 )

• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

Genotype
MGI:3042284

hm2

• Allelic Composition: Fst^tm1Zuk/Fst^tm1Zuk
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

neonatal lethality, complete penetrance ( J:23925 )

• homozygotes survive to birth but die within a few hours of birth due to respiratory failure

craniofacial

growth retardation of incisors ( J:23925 )

• all newborn homozygotes (11 of 11) show delayed development of lower incisors

absent hard palate ( J:23925 )

• 55% (6 of 11) newborn homozygotes lack a hard palate

growth/size/body

growth retardation of incisors ( J:23925 )

• all newborn homozygotes (11 of 11) show delayed development of lower incisors

absent hard palate ( J:23925 )

• 55% (6 of 11) newborn homozygotes lack a hard palate

decreased fetal size ( J:23925 )

• at E18.5, homozygotes are smaller than wild-type counterparts

decreased fetal weight ( J:23925 )

• at E18.5, homozygotes weigh ~12% less than wild-type counterparts

fetal growth retardation ( J:23925 )

• newborn homozygotes are growth retarded

muscle

decreased skeletal muscle mass ( J:23925 )

• newborn homozygotes show decreased muscle mass in the diaphragmatic, pectoralis major and intercostal muscles

• however, no primary defects are observed as determined by analysis of ATPase activity, glycogen content and mitochondria

skeleton

growth retardation of incisors ( J:23925 )

• all newborn homozygotes (11 of 11) show delayed development of lower incisors

abnormal rib development ( J:23925 )

• in 81.8% (9 of 11) homozygotes, development of the thirteenth pair of ribs is limited

• Background Sensitivity: a higher percentage of homozygotes show limited formation of the thirteenth rib pair on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (81.8% vs 61%, respectively)

decreased rib number ( J:23925 )

• in 2 of 11 homozygotes, the thirteenth pair of ribs is absent

decreased lumbar vertebrae number ( J:23925 )

• all (11 of 11) newborn homozygotes have five lumbar vertebrae instead of six found in wild-type mice

digestive/alimentary system

absent hard palate ( J:23925 )

• 55% (6 of 11) newborn homozygotes lack a hard palate

homeostasis/metabolism

cyanosis ( J:23925 )

• newborn homozygotes appear cyanotic

respiratory system

respiratory failure ( J:23925 )

• newborn homozygotes fail to breathe

• mutant lungs are sank in liquid, and alveolar spaces appear poorly expanded, although no primary pulmonary defects are detected

integument

abnormal vibrissa morphology ( J:23925 )

• mutant whiskers are very thin and incorrectly oriented with shafts projecting parallel before turning perpendicularly

hyperkeratosis ( J:23925 )

• newborns display a 25% increase in the stratum corneum cells relative to wild-type controls

thick epidermis ( J:23925 )

• newborn homozygotes show a thickened granular and stratum corneum

pallor ( J:23925 )

• newborn homozygotes appear hypoxic (pale)

shiny skin ( J:23925 )

• newborn homozygotes display a shiny skin

tight skin ( J:23925 )

• newborn homozygotes display a taut skin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
restrictive dermopathy		DOID:0060762	OMIM:PS275210	J:23925

Genotype
MGI:3042286

hm3

• Allelic Composition: Fst^tm1Zuk/Fst^tm1Zuk
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:23925 )

• homozygotes survive to birth but die within a few hours of birth due to respiratory failure

craniofacial

absent lower incisors ( J:23925 )

• 6 of 34 newborn homozygotes lack lower incisors

growth retardation of incisors ( J:23925 )

• 92% (23 of 34) newborn homozygotes show delayed development of lower incisors

absent hard palate ( J:23925 )

• 21.4% (6 of 28) newborn homozygotes lack a hard palate

cleft secondary palate ( J:23925 )

• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate

growth/size/body

absent lower incisors ( J:23925 )

• 6 of 34 newborn homozygotes lack lower incisors

growth retardation of incisors ( J:23925 )

• 92% (23 of 34) newborn homozygotes show delayed development of lower incisors

absent hard palate ( J:23925 )

• 21.4% (6 of 28) newborn homozygotes lack a hard palate

cleft secondary palate ( J:23925 )

• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate

decreased fetal size ( J:23925 )

• at E18.5, homozygotes are smaller than wild-type counterparts

decreased fetal weight ( J:23925 )

• at E18.5, homozygotes weigh ~12% less than wild-type counterparts

fetal growth retardation ( J:23925 )

• newborn homozygotes are growth retarded

muscle

decreased skeletal muscle mass ( J:23925 )

• newborn homozygotes show decreased muscle mass in the diaphragmatic, pectoralis major and intercostal muscles

• however, no primary defects are observed as determined by analysis of ATPase activity, glycogen content and mitochondria

skeleton

absent lower incisors ( J:23925 )

• 6 of 34 newborn homozygotes lack lower incisors

growth retardation of incisors ( J:23925 )

• 92% (23 of 34) newborn homozygotes show delayed development of lower incisors

abnormal sternocostal joint morphology ( J:23925 )

• in 4 of 28 homozygotes, one or both of the seventh ribs fail to fuse to the sternum

abnormal rib development ( J:23925 )

• in 61% (17 of 28) homozygotes, development of the thirteenth pair of ribs is limited

• Background Sensitivity: a higher percentage of homozygotes show limited formation of the thirteenth rib pair on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (81.8% vs 61%, respectively)

decreased rib number ( J:23925 )

• in 28.6% (8 of 28) homozygotes, the thirteenth pair of ribs is absent

decreased lumbar vertebrae number ( J:23925 )

• all (28 of 28) newborn homozygotes have five lumbar vertebrae instead of six; only 2 of 15 wild-type controls show this defect

digestive/alimentary system

absent hard palate ( J:23925 )

• 21.4% (6 of 28) newborn homozygotes lack a hard palate

cleft secondary palate ( J:23925 )

• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate

homeostasis/metabolism

cyanosis ( J:23925 )

• newborn homozygotes appear cyanotic

respiratory system

respiratory failure ( J:23925 )

• newborn homozygotes fail to breathe

• mutant lungs are sank in liquid, and alveolar spaces appear poorly expanded, although no primary pulmonary defects are detected

integument

abnormal vibrissa morphology ( J:23925 )

• mutant whiskers are very thin and incorrectly oriented with shafts projecting parallel before turning perpendicularly

hyperkeratosis ( J:23925 )

• newborns display a 25% increase in the stratum corneum cells relative to wild-type controls

thick epidermis ( J:23925 )

• newborn homozygotes show a thickened granular and stratum corneum

pallor ( J:23925 )

• newborn homozygotes appear hypoxic (pale)

shiny skin ( J:23925 )

• newborn homozygotes display a shiny skin

tight skin ( J:23925 )

• newborn homozygotes display a taut skin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
restrictive dermopathy		DOID:0060762	OMIM:PS275210	J:23925

Genotype
MGI:5319775

ht4

• Allelic Composition: Fst^tm1Zuk/Fst⁺
• Genetic Background: B6.129S7-Fst^tm1Zuk

muscle

abnormal extensor digitorum longus morphology ( J:182827 )

• increase in the percentage of oxidative type I fibers

decreased quadriceps weight ( J:182827 )

abnormal gastrocnemius morphology ( J:182827 )

• increase in the number of oxidative type I fibers

decreased gastrocnemius weight ( J:182827 )

abnormal skeletal muscle fiber morphology ( J:182827 )

• decrease in mean fiber diameter for each fiber type

• increase in the proportion of smaller fibers that stain more darkly in hematoxylin and eosin stained sections corresponding to mixed glycolytic/oxidative type IIa fibers

• shift towards more oxidative fibers

decreased skeletal muscle weight ( J:182827 )

• about 15-20% lower than wild-type

• decreased triceps weight

abnormal pectoral muscle morphology ( J:182827 )

• decreased weight

abnormal muscle physiology ( J:182827 )

• lower twitch and tetanic force production

• but no change in specific force

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:182827 )

• impaired muscle regeneration and enhanced fibrosis in the gastrocnemius muscle following cardiotoxin-induced injury

limbs/digits/tail

abnormal extensor digitorum longus morphology ( J:182827 )

• increase in the percentage of oxidative type I fibers

decreased quadriceps weight ( J:182827 )

abnormal gastrocnemius morphology ( J:182827 )

• increase in the number of oxidative type I fibers

decreased gastrocnemius weight ( J:182827 )

Genotype
MGI:3814734

ht5

• Allelic Composition: Fst^tm1Zuk/Fst⁺
• Genetic Background: involves: 129S7/SvEvBrd

skeleton

abnormal rib development ( J:23925 )

• in 26.6% (4 of 15) heterozygotes, development of the thirteenth pair of ribs is limited; not oberved in wild-type controls

• Background Sensitivity: a higher percentage of heterozygotes show limited formation of the thirteenth rib pair on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (26.6% vs 17%, respectively)

decreased lumbar vertebrae number ( J:23925 )

• 86.6% (13 of 15) heterozygotes have five lumbar vertebrae instead of six found in wild-type controls

• Background Sensitivity: a higher percentage of heterozygotes show five lumbar vertebrae on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (86.6% vs 60%, respectively)

Genotype
MGI:3814735

ht6

• Allelic Composition: Fst^tm1Zuk/Fst⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

skeleton

abnormal rib development ( J:23925 )

• in 17% (6 of 35) heterozygotes, development of the thirteenth pair of ribs is limited; not oberved in wild-type controls

• Background Sensitivity: a higher percentage of heterozygotes show limited formation of the thirteenth rib pair on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (26.6% vs 17%, respectively)

decreased lumbar vertebrae number ( J:23925 )

• 60% (21 of 35) heterozygotes have five lumbar vertebrae instead of six; only 2 of 15 wild-type controls show this defect

• Background Sensitivity: a higher percentage of heterozygotes show five lumbar vertebrae on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (86.6% vs 60%, respectively)

Genotype
MGI:3042275

cn7

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Fst^tm1Zuk/Fst^tm2Zuk
• Genetic Background: involves: 129S/SvEv * C57BL/6J

endocrine/exocrine glands

ovary hemorrhage ( J:89081 )

♀ • the majority of ovaries in 8 month old mice appeared hemorrhagic

abnormal ovary morphology ( J:89081 )

♀ • ovaries were histologically normal through 21 days of age

♀ • defects became apparent after 3 months of age

decreased corpora lutea number ( J:89081 )

♀ • some mice developed Sertoli cell tubule-like structures, reminiscent of the ovarian tumors observed in mice inhibin-deficient mice, mice overexpressing follistatin and follicle stimulating hormone, mice lacking both estrogen receptors alpha and beta, and mice overexpressing anti-Mullerian hormone

decreased tertiary ovarian follicle number ( J:89081 )

♀ • decreased numbers of antral follicles

ovary cyst ( J:89081 )

♀ • observed in 2 mice

growth/size/body

ovary cyst ( J:89081 )

♀ • observed in 2 mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:89081 )

N • circulating estradiol levels did not differ from those of controls

decreased circulating testosterone level ( J:89081 )

increased circulating follicle stimulating hormone level ( J:89081 )

increased circulating luteinizing hormone level ( J:89081 )

reproductive system

reproductive system phenotype ( J:89081 )

N • male mice were fertile

ovary hemorrhage ( J:89081 )

♀ • the majority of ovaries in 8 month old mice appeared hemorrhagic

abnormal ovary morphology ( J:89081 )

♀ • ovaries were histologically normal through 21 days of age

♀ • defects became apparent after 3 months of age

decreased corpora lutea number ( J:89081 )

♀ • some mice developed Sertoli cell tubule-like structures, reminiscent of the ovarian tumors observed in mice inhibin-deficient mice, mice overexpressing follistatin and follicle stimulating hormone, mice lacking both estrogen receptors alpha and beta, and mice overexpressing anti-Mullerian hormone

decreased tertiary ovarian follicle number ( J:89081 )

♀ • decreased numbers of antral follicles

ovary cyst ( J:89081 )

♀ • observed in 2 mice

decreased superovulation rate ( J:89081 )

♀ • impaired ovulation in response to human chorionic gonadotropin (hCG) only in mature adult mice (6 months of age)

♀ • however, superovulation was normal in 3-week-old mice

female infertility ( J:89081 )

♀ • of 11 female experimental mice, 1 was completely infertile

reduced female fertility ( J:89081 )

♀ • of 11 female experimental mice, 10 showed reduced fertility, yielding reduced litter number and size

decreased litter size ( J:89081 )

impaired fertilization ( J:89081 )

• impaired fertilization only in mature adult mice (6 months of age)

• fertilization was normal in 3-week-old mice

cardiovascular system

ovary hemorrhage ( J:89081 )

♀ • the majority of ovaries in 8 month old mice appeared hemorrhagic

Genotype
MGI:5319774

cx8

• Allelic Composition: Fst^tm1Zuk/Fst⁺; Fstl3^tm1.1Sjl/Fstl3^tm1.1Sjl
• Genetic Background: B6.129-Fst^tm1Zuk Fstl3^tm1.1Sjl

muscle

decreased skeletal muscle weight ( J:182827 )

• similar to mice heterozygous for Fst^tm1Zuk alone

Genotype
MGI:5319777

cx9

• Allelic Composition: Fst^tm1Zuk/Fst⁺; Mstn^tm1Sjl/Mstn⁺
• Genetic Background: B6.129-Mstn^tm1Sjl Fst^tm1Zuk

muscle

decreased skeletal muscle weight ( J:182827 )

• relative to mice heterozygous for Mstn^tm1Sjl alone

growth/size/body

decreased body weight ( J:182827 )

• relative to mice heterozygous for Mstn^tm1Sjl alone

Genotype
MGI:5319776

cx10

• Allelic Composition: Fst^tm1Zuk/Fst⁺; Mstn^tm1Sjl/Mstn^tm1Sjl
• Genetic Background: B6.129-Mstn^tm1Sjl Fst^tm1Zuk

muscle

decreased skeletal muscle weight ( J:182827 )

• relative to mice homoozygous for Mstn^tm1Sjl alone

Genotype
MGI:5546336

cx11

• Allelic Composition: Fst^tm1Zuk/Fst^tm1Zuk; Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Axial skeleton patterning defects in Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl, Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl Fst^tm1Zuk/Fst^tm1Zuk, Gdf11^tm1Sjl/Gdf11⁺ and Gdf11^tm1Sjl/Gdf11^tm1Sjl mice.

skeleton

abnormal cervical rib ( J:201148 )

• mice have cervical ribs on one side or both sides

decreased rib number ( J:201148 )

• both 13th ribs are missing

• most mice have 6 or 6.5 attached ribs

increased rib number ( J:201148 )

• mice have cervical ribs on one side or both sides

decreased thoracic vertebrae number ( J:201148 )

• all mice have only 12 thoracic vertebrae

decreased lumbar vertebrae number ( J:201148 )

• one mouse had only 4 lumbar vertebrae

Genotype
MGI:5546337

cx12

• Allelic Composition: Fst^tm1Zuk/Fst⁺; Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Axial skeleton patterning defects in Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl, Wfikkn1^tm1.1Sjl/Wfikkn1^tm1.1Sjl Fst^tm1Zuk/Fst^tm1Zuk, Gdf11^tm1Sjl/Gdf11⁺ and Gdf11^tm1Sjl/Gdf11^tm1Sjl mice.

skeleton

abnormal cervical rib ( J:201148 )

• cervical ribs are seen on one or both sides in most mice

decreased rib number ( J:201148 )

• over 90% of mice are missing both 13th ribs

increased rib number ( J:201148 )

• cervical ribs are seen on one or both sides in most mice

decreased thoracic vertebrae number ( J:201148 )

• most mice have 12 thoracic vertebrae

increased lumbar vertebrae number ( J:201148 )

• 25% of mice have 6/7 lumbar vertebrae

Genotype
MGI:5546338

cx13

• Allelic Composition: Fst^tm1Zuk/Fst^tm1Zuk; Wfikkn1^tm1.1Sjl/Wfikkn1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

skeleton

decreased rib number ( J:201148 )

• 50% of mice have only 12 thoracic vertebrae

decreased thoracic vertebrae number ( J:201148 )

• in 50% of mice the 13th pair of ribs consist of one anlage and the other is absent and in the other 50% of mice both 13th ribs are missing

Genotype
MGI:3589668

cx14

• Allelic Composition: Fst^tm1Zuk/Fst^tm1Zuk; Gdf11^tm1Clf/Gdf11^tm1Clf
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * CD-1

nervous system

increased retina ganglion cell number ( J:99244 )

• double mutant retinas display an expanded differentiated ganglion cell layer, similar to that observed in Gdf11^tm1Clf mutant retinas

• at E17.5, the neuroblastic layer of double mutant retinas shows a 3-fold increase in migrating ganglion cells relative to wild-type retinas

vision/eye

abnormal retina neuronal layer morphology ( J:99244 )

increased retina ganglion cell number ( J:99244 )

• double mutant retinas display an expanded differentiated ganglion cell layer, similar to that observed in Gdf11^tm1Clf mutant retinas

• at E17.5, the neuroblastic layer of double mutant retinas shows a 3-fold increase in migrating ganglion cells relative to wild-type retinas