Mouse Genome Informatics
hm1
    Fsttm1Zuk/Fsttm1Zuk
B6.129S7-Fsttm1Zuk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• homozygotes display decreased olfactory epithelium neurogenesis, as shown by significantly reduced neurogenin-1-expressing immediate neuronal precursors and Ncam1-expressing olfactory receptor neurons
• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

taste/olfaction
• homozygotes display a 38% decrease in thickness of the olfactory epithelium
• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

vision/eye
• 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
• homozygotes display a 38% decrease in thickness of the olfactory epithelium
• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

craniofacial
• homozygotes display a 38% decrease in thickness of the olfactory epithelium
• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium

cellular
• 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
• homozygotes display a 38% decrease in thickness of the olfactory epithelium
• at E17.5, homozygotes display a 37% decrease in proliferating, neurogenin-1-expressing immediate neuronal precursors within the olfactory epithelium


Mouse Genome Informatics
hm2
    Fsttm1Zuk/Fsttm1Zuk
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes survive to birth but die within a few hours of birth due to respiratory failure

craniofacial
• all newborn homozygotes (11 of 11) show delayed development of lower incisors
• 55% (6 of 11) newborn homozygotes lack a hard palate

growth/size
• all newborn homozygotes (11 of 11) show delayed development of lower incisors
• 55% (6 of 11) newborn homozygotes lack a hard palate
• at E18.5, homozygotes are smaller than wild-type counterparts
• at E18.5, homozygotes weigh ~12% less than wild-type counterparts
• newborn homozygotes are growth retarded

muscle
• 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
• 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)
• in 2 of 11 homozygotes, the thirteenth pair of ribs is absent
• all (11 of 11) newborn homozygotes have five lumbar vertebrae instead of six found in wild-type mice

digestive/alimentary system
• 55% (6 of 11) newborn homozygotes lack a hard palate

homeostasis/metabolism
• newborn homozygotes appear cyanotic

respiratory system
• 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
• mutant whiskers are very thin and incorrectly oriented with shafts projecting parallel before turning perpendicularly
• newborns display a 25% increase in the stratum corneum cells relative to wild-type controls
• newborn homozygotes show a thickened granular and stratum corneum
• newborn homozygotes appear hypoxic (pale)
• newborn homozygotes display a shiny skin
• newborn homozygotes display a taut skin

Mouse Models of Human Disease
OMIM IDRef(s)
Restrictive Dermopathy, Lethal 275210 J:23925


Mouse Genome Informatics
hm3
    Fsttm1Zuk/Fsttm1Zuk
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes survive to birth but die within a few hours of birth due to respiratory failure

craniofacial
• 92% (23 of 34) newborn homozygotes show delayed development of lower incisors
• 21.4% (6 of 28) newborn homozygotes lack a hard palate
• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate
• 6 of 34 newborn homozygotes lack lower incisors

growth/size
• 92% (23 of 34) newborn homozygotes show delayed development of lower incisors
• 21.4% (6 of 28) newborn homozygotes lack a hard palate
• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate
• 6 of 34 newborn homozygotes lack lower incisors
• at E18.5, homozygotes are smaller than wild-type counterparts
• at E18.5, homozygotes weigh ~12% less than wild-type counterparts
• newborn homozygotes are growth retarded

muscle
• 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
• in 4 of 28 homozygotes, one or both of the seventh ribs fail to fuse to the sternum
• 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)
• in 61% (17 of 28) homozygotes, development of the thirteenth pair of ribs is limited
• in 28.6% (8 of 28) homozygotes, the thirteenth pair of ribs is absent
• 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
• 21.4% (6 of 28) newborn homozygotes lack a hard palate
• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate

homeostasis/metabolism
• newborn homozygotes appear cyanotic

respiratory system
• 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
• mutant whiskers are very thin and incorrectly oriented with shafts projecting parallel before turning perpendicularly
• newborns display a 25% increase in the stratum corneum cells relative to wild-type controls
• newborn homozygotes show a thickened granular and stratum corneum
• newborn homozygotes appear hypoxic (pale)
• newborn homozygotes display a shiny skin
• newborn homozygotes display a taut skin

Mouse Models of Human Disease
OMIM IDRef(s)
Restrictive Dermopathy, Lethal 275210 J:23925


Mouse Genome Informatics
ht4
    Fsttm1Zuk/Fst+
B6.129S7-Fsttm1Zuk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• 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
• decrease in mean fiber diameter for each fiber type
• about 15-20% lower than wild-type
• decreased triceps weight
• increase in the percentage of oxidative type I fibers
• increase in the number of oxidative type I fibers
• lower twitch and tetanic force production
• but no change in specific force

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


Mouse Genome Informatics
ht5
    Fsttm1Zuk/Fst+
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• 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)
• 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)


Mouse Genome Informatics
ht6
    Fsttm1Zuk/Fst+
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• 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)
• 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)


Mouse Genome Informatics
cn7
    Amhr2tm3(cre)Bhr/Amhr2+
Fsttm1Zuk/Fsttm2Zuk

involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• the majority of ovaries in 8 month old mice appeared hemorrhagic (J:89081)
• ovaries were histologically normal through 21 days of age (J:89081)
• defects became apparent after 3 months of age (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 (J:89081)
• decreased numbers of antral follicles (J:89081)
• observed in 2 mice (J:89081)

homeostasis/metabolism
N
• circulating estradiol levels did not differ from those of controls (J:89081)

reproductive system
N
• male mice were fertile (J:89081)
• the majority of ovaries in 8 month old mice appeared hemorrhagic (J:89081)
• ovaries were histologically normal through 21 days of age (J:89081)
• defects became apparent after 3 months of age (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 (J:89081)
• decreased numbers of antral follicles (J:89081)
• observed in 2 mice (J:89081)
• impaired ovulation in response to human chorionic gonadotropin (hCG) (J:89081)
• impaired only in mature adult mice (6 months of age), ovulation was normal in 3 week old mice (J:89081)
• of 11 female experimental mice, 1 was completely infertile (J:89081)
• of 11 female experimental mice, 10 showed reduced fertility, yielding reduced litter number and size (J:89081)
• impaired only in mature adult mice (6 months of age), fertilization was normal in 3 week old mice

cardiovascular system
• the majority of ovaries in 8 month old mice appeared hemorrhagic (J:89081)


Mouse Genome Informatics
cx8
    Fsttm1Zuk/Fst+
Fstl3tm1.1Sjl/Fstl3tm1.1Sjl

B6.129-Fsttm1Zuk Fstl3tm1.1Sjl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• similar to mice heterozygous for Fsttm1Zuk alone


Mouse Genome Informatics
cx9
    Fsttm1Zuk/Fst+
Mstntm1Sjl/Mstntm1Sjl

B6.129-Mstntm1Sjl Fsttm1Zuk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• relative to mice homoozygous for Mstntm1Sjl alone


Mouse Genome Informatics
cx10
    Fsttm1Zuk/Fst+
Mstntm1Sjl/Mstn+

B6.129-Mstntm1Sjl Fsttm1Zuk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• relative to mice heterozygous for Mstntm1Sjl alone

growth/size
• relative to mice heterozygous for Mstntm1Sjl alone


Mouse Genome Informatics
cx11
    Fsttm1Zuk/Fsttm1Zuk
Wfikkn1tm1.1Sjl/Wfikkn1tm1.1Sjl

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• mice have cervical ribs on one side or both sides
• both 13th ribs are missing
• most mice have 6 or 6.5 attached ribs
• mice have cervical ribs on one side or both sides
• all mice have only 12 thoracic vertebrae
• one mouse had only 4 lumbar vertebrae


Mouse Genome Informatics
cx12
    Fsttm1Zuk/Fst+
Wfikkn1tm1.1Sjl/Wfikkn1tm1.1Sjl

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• cervical ribs are seen on one or both sides in most mice
• over 90% of mice are missing both 13th ribs
• cervical ribs are seen on one or both sides in most mice
• most mice have 12 thoracic vertebrae
• 25% of mice have 6/7 lumbar vertebrae


Mouse Genome Informatics
cx13
    Fsttm1Zuk/Fsttm1Zuk
Wfikkn1tm1.1Sjl/Wfikkn1+

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• 50% of mice have only 12 thoracic vertebrae
• 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


Mouse Genome Informatics
cx14
    Fsttm1Zuk/Fsttm1Zuk
Gdf11tm1Clf/Gdf11tm1Clf

involves: 129X1/SvJ * C57BL/6J * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• double mutant retinas display an expanded differentiated ganglion cell layer, similar to that observed in Gdf11tm1Clf 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
• double mutant retinas display an expanded differentiated ganglion cell layer, similar to that observed in Gdf11tm1Clf 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