All Phenotypes Mrps22<tm1.1(KOMP)Vlcg> MGI Mouse

embryonic lethality between implantation and placentation, complete penetrance ( J:290315 , J:279207 )

• although homozygous embryos are recovered at expected Mendelian ratios at E7.5, decidua with embryo resorptions are detected at E8.5 (J:290315)

• homozygous embryos are recovered at expected Mendelian ratios at E7.5 but arrest prior to gastrulation; no homozygous embryos are recovered at E9.5 (J:279207)

failure to gastrulate ( J:290315 , J:279207 )

• no structures typical of gastrulation are observed at E7.5 (J:290315)

• no morphological hallmarks of gastrulation are observed at E7.5 (J:279207)

embryonic growth arrest ( J:290315 , J:279207 )

• embryos stall at about the size of wild-type E6.0 embryos, just prior to the onset of gastrulation; only two cell layers with bilaterally symmetric egg-cylinder morphology are seen at E7.5 (J:290315)

• however, no disorganization or pyknotic/dying cells are apparent at E7.5 (J:290315)

• embryos arrest prior to gastrulation (J:279207)

embryonic growth retardation ( J:290315 , J:279207 )

• at E7.5, embryos are significantly delayed and appear as relatively pristine early egg-cylinder stage embryos (J:290315)

• however, no widespread active Trp53-positive apoptotic cells are detected at E7.5 (J:290315)

• at E7.5, embryos are developmentally delayed (~E6.0 size) (J:279207)

• however, many phospho-histoneH3 (PH3)-positive dividing cells are present (J:279207)

decreased embryo size ( J:290315 )

• at E7.5, embryos are dramatically smaller than controls

abnormal embryonic epiblast morphology ( J:290315 )

• at E7.5, embryos still retain robust nuclear Pou5f/Oct4 signal in the epiblast

absent head fold ( J:290315 )

• no morphological head folds are evident at E7.5

absent primitive node ( J:290315 )

• no morphological nodes are evident at E7.5

failure of primitive streak formation ( J:290315 , J:279207 )

• no morphological primitive streak or Brachyury (T)-positive cells are detected at E7.5 (J:290315)

• no Brachyury (T)-positive cells are observed at E7.5, suggesting failure to initiate primitive streak formation (J:279207)

absent allantois ( J:290315 )

• no morphological allantois is evident at E7.5

embryonic growth retardation ( J:290315 , J:279207 )

• at E7.5, embryos are significantly delayed and appear as relatively pristine early egg-cylinder stage embryos (J:290315)

• however, no widespread active Trp53-positive apoptotic cells are detected at E7.5 (J:290315)

• at E7.5, embryos are developmentally delayed (~E6.0 size) (J:279207)

• however, many phospho-histoneH3 (PH3)-positive dividing cells are present (J:279207)

decreased embryo size ( J:290315 )

• at E7.5, embryos are dramatically smaller than controls

cellular phenotype ( J:290315 )

N	• embryos show no significant differences in 4HNE (4-hydroxynonenal) levels or localization relative to wild-type controls, suggesting no increase in lipid peroxidation or oxidative stress

decreased cellular ATP level ( J:290315 )

• embryos show a significantly higher ADP to ATP ratio, indicating mitochondrial dysfunction

abnormal mitochondrial morphology ( J:290315 )

• at E7.5, TEM shows a marked alteration in mitochondrial morphology, with many large vesicle-like structures present within every mitochondrion

• however, the ratio of mitochondrial to nuclear genome content is similar to that in control embryos and only a slight increase in caspase-3 mediated apoptosis is noted in the embryonic portion

abnormal mitochondrial crista morphology ( J:290315 )

• mitochondria exhibit far fewer cristae at E7.5

abnormal cell cycle checkpoint function ( J:290315 )

• embryo sections show increased numbers of bright pH3 foci (pH3, a marker of dividing cells) relative to controls, suggesting that cells arrest in the G2/late G2 phase

• analysis of the phosphorylation status of Cdc25c (cell division cycle 25C) at serine 216 (S216) shows that embryos exhibit significantly more phospho-Cdc25c foci than littermates and stage-matched controls, indicating cell cycle arrest at the G2/M checkpoint

abnormal mitochondrial physiology ( J:290315 )

• embryos show a significantly higher ADP to ATP ratio, indicating mitochondrial dysfunction

abnormal respiratory electron transport chain ( J:290315 )

• mitochondrial translation is impaired leading to a lack of ETC related proteins, as indicated by the absence of MT-CO2 protein (mitochondrially encoded cytochrome c oxidase II) in embryonic cells

abnormal mitochondrial ATP synthesis coupled electron transport ( J:290315 )

• absence of functional ETC components is likely responsible for the drastic reduction of ATP production

decreased cellular ATP level ( J:290315 )

• embryos show a significantly higher ADP to ATP ratio, indicating mitochondrial dysfunction

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

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

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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