Phenotypes associated with this allele

• Allele Symbol: Mettl1^em1Bcgen
• Allele Name: endonuclease-mediated mutation 1, Biocytogen LLC
• Allele ID: MGI:7859737
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mettl1^em1Bcgen/Mettl1^em1Bcgen Tsc1^tm1Djk/Tsc1^tm1Djk Tg(Prrx1-cre)1Cjt/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * SJL/J	MGI:7860786
cn2	Mettl1^em1Bcgen/Mettl1^em1Bcgen Tg(Prrx1-cre)1Cjt/0	involves: C57BL/6J * SJL/J	MGI:7859766
cn3	Eif2ak4^em14Gpt/Eif2ak4^em14Gpt Mettl1^em1Bcgen/Mettl1^em1Bcgen Tg(Prrx1-cre)1Cjt/0	involves: C57BL/6 * SJL/J	MGI:7860785

Genotype
MGI:7860786

cn1

• Allelic Composition: Mettl1^em1Bcgen/Mettl1^em1Bcgen; Tsc1^tm1Djk/Tsc1^tm1Djk; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * SJL/J

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

limbs/digits/tail

abnormal autopod morphology ( J:355649 )

• autopod formation is more severely ratarded than in mutant mice wild-type for Tsc1

short limbs ( J:355649 )

• limb shortening is more severe than in mice wild-type for Tsc1

• length of stylopod and zeugopod is further shortened compared to mutant mice wild-type for Tsc1

skeleton

decreased bone mineralization ( J:355649 )

• hypocalcified humerus

Genotype
MGI:7859766

cn2

• Allelic Composition: Mettl1^em1Bcgen/Mettl1^em1Bcgen; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: C57BL/6J * SJL/J

limbs/digits/tail

short humerus ( J:355649 )

• at E16.5 length is reduced

short femur ( J:355649 )

• at P21

short limbs ( J:355649 )

• severe shortening of the limbs at birth

• proportional shortening of all limb skeletal elements is present at E18.5 and P0

• supplementing damns with alpha-ketoglutarate increases the length of limbs in newborn pups

skeleton

decreased chondrocyte proliferation ( J:355649 )

• reduced proliferation of chondrocytes on the proliferating zone of the growth plate

• however, apoptosis of chondrocytes is similar to controls

short humerus ( J:355649 )

• at E16.5 length is reduced

short femur ( J:355649 )

• at P21

decreased width of hypertrophic chondrocyte zone ( J:355649 )

• marked reduction of the hypertrophic zone at E14.5, E18.5, and P7

• supplementing damns with alpha-ketoglutarate increases the length of the growth plate hypertrophic zones

decreased bone mineral density of femur ( J:355649 )

• at P21

abnormal osteoblast morphology ( J:355649 )

• decrease in the number of osteoblast precursors in the primary ossification centers of the humerus at E16.5

abnormal trabecular bone morphology ( J:355649 )

decreased trabecular bone volume ( J:355649 )

• decreased trabecular bone volume per tissue volume in the distal femur

decreased bone trabecula number ( J:355649 )

• in the distal femur

increased bone trabecular spacing ( J:355649 )

• in the distal femur

decreased trabecular bone thickness ( J:355649 )

• in the distal femur

abnormal chondrocyte morphology ( J:355649 )

• chrondrocytes fail to undergo hypertrophy and form secondary ossification centers at P21 in the femurs

abnormal bone ossification ( J:355649 )

decreased bone mineralization ( J:355649 )

• stylopod and zeugopod are normal in length but appear hypomineralized at E14.5

• hypomineralization of the humerus at E16.5

• impaired matrix mineralization in humeral sections at E18.5

abnormal endochondral bone ossification ( J:355649 )

• at P7 chondrocytes remain small and round rather than undergoing hypertrophy and forming a secondary ossification center as in littermate controls

• at P21 the secondary ossification center has not formed in the femors

decreased bone ossification ( J:355649 )

• cultured skeletal stem cells induced toward osteogenic differentiation show reduced alkaline phosphatase activity and calcium nodule deposition

growth/size/body

decreased body size ( J:355649 )

• at P21

homeostasis/metabolism

increased cellular ATP level ( J:355649 )

• increased steady state ATP levels

increased oxygen consumption ( J:355649 )

• elevated maximal but not basal O2 consumption rate

cellular

increased cellular ATP level ( J:355649 )

• increased steady state ATP levels

abnormal cell physiology ( J:355649 )

• elevated intracellular lactate in cells and increased lactate secretion

• increase in glycolysis

decreased chondrocyte proliferation ( J:355649 )

• reduced proliferation of chondrocytes on the proliferating zone of the growth plate

• however, apoptosis of chondrocytes is similar to controls

decreased cellular glucose uptake ( J:355649 )

abnormal cellular respiration ( J:355649 )

• expression analysis shows a metabolic active state

• increase of ATP and phosphocreatine and reduction of ADP in isolated limb mesenchymal cells

abnormal mitochondrial physiology ( J:355649 )

• slight increase in ROS production

Genotype
MGI:7860785

cn3

• Allelic Composition: Eif2ak4^em14Gpt/Eif2ak4^em14Gpt; Mettl1^em1Bcgen/Mettl1^em1Bcgen; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: C57BL/6 * SJL/J

limbs/digits/tail

short limbs ( J:355649 )

• limb shortening is more severe than in controls with one wild-type Eif2ak4 allele