Mouse copper-transporting ATPase Atp7a

evidence_span

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experimental_model

Atp7a silencing and orthotopic tumor experiments

exposure

Atp7a silencing

limitations

Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse; separate human survival association

plain_language

The copper delivery pump helps activate extracellular cross-linking enzymes.

primary_references

[copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116

tissue_or_cell_type

4T1 mammary carcinoma and Lewis lung carcinoma

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 923–934

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atp7a silencing and orthotopic tumor experiments · source_derived_draft · unverified_draft

### copper-atp7a-lox-loading Atp7a silencing reduced LOX/LOXL activity in mouse mammary and lung carcinoma models. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper delivery pump helps activate extracellular cross-linking enzymes. organism: Mouse; separate human survival association tissue_or_cell_type: 4T1 mammary carcinoma and Lewis lung carcinoma experimental_model: Atp7a silencing and orthotopic tumor experiments limitations: Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative. exposure: Atp7a silencing evidence_span: {"source_cache": "artifacts/copper-research/30890638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816", "start_char": 0, "end_char": 1001, "text_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816"} [copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116

evidence_span

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experimental_model

Atp7a silencing and orthotopic tumor experiments

exposure

Atp7a silencing

limitations

Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse; separate human survival association

plain_language

A normal tissue-building pathway can be used by tumors in a different context.

primary_references

[copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116

tissue_or_cell_type

4T1 mammary carcinoma and Lewis lung carcinoma

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 936–947

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atp7a silencing and orthotopic tumor experiments · source_derived_draft · unverified_draft

### copper-atp7a-lox-metastasis Atp7a silencing reduced LOX-associated metastatic behavior, including focal-adhesion signaling and lung myeloid recruitment in the tested mammary tumor model. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal tissue-building pathway can be used by tumors in a different context. organism: Mouse; separate human survival association tissue_or_cell_type: 4T1 mammary carcinoma and Lewis lung carcinoma experimental_model: Atp7a silencing and orthotopic tumor experiments limitations: Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative. exposure: Atp7a silencing evidence_span: {"source_cache": "artifacts/copper-research/30890638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816", "start_char": 0, "end_char": 1001, "text_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816"} [copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"}

experimental_model

Genetic and streptozotocin diabetes mouse models with vascular rescue assays

exposure

Diabetes, Atp7a overexpression, copper or insulin ex vivo

limitations

Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

Restoring copper delivery improved the enzyme’s activity.

primary_references

[copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228

tissue_or_cell_type

Aortas, mesenteric vessels and vascular smooth muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 949–960

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and streptozotocin diabetes mouse models with vascular rescue assays · source_derived_draft · unverified_draft

### copper-atp7a-sod3 Atp7a overexpression restored reduced SOD3 specific activity in diabetic mouse vessels. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring copper delivery improved the enzyme’s activity. organism: Mouse tissue_or_cell_type: Aortas, mesenteric vessels and vascular smooth muscle experimental_model: Genetic and streptozotocin diabetes mouse models with vascular rescue assays limitations: Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect. exposure: Diabetes, Atp7a overexpression, copper or insulin ex vivo evidence_span: {"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"} [copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228

evidence_span

{"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"}

experimental_model

Mouse melanocyte localization and tyrosinase metallation experiments

exposure

ATP7A/BLOC-1-dependent localization

limitations

Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

The pigment enzyme needs copper at its final workplace, not just earlier during production.

primary_references

[copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163

tissue_or_cell_type

Golgi and melanosomes

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 988–999

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse melanocyte localization and tyrosinase metallation experiments · source_derived_draft · unverified_draft

### copper-atp7a-tyr-reloading Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pigment enzyme needs copper at its final workplace, not just earlier during production. organism: Mouse tissue_or_cell_type: Golgi and melanosomes experimental_model: Mouse melanocyte localization and tyrosinase metallation experiments limitations: Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency. exposure: ATP7A/BLOC-1-dependent localization evidence_span: {"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"} [copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"}

experimental_model

Genetic and streptozotocin diabetes mouse models with vascular rescue assays

exposure

Diabetes, Atp7a overexpression, copper or insulin ex vivo

limitations

Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

Hormone signaling can change whether a copper-dependent enzyme receives its metal.

primary_references

[copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228

tissue_or_cell_type

Aortas, mesenteric vessels and vascular smooth muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 975–986

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and streptozotocin diabetes mouse models with vascular rescue assays · source_derived_draft · unverified_draft

### copper-insulin-atp7a Insulin treatment increased ATP7A expression in vascular smooth muscle cells and restored SOD3 activity in diabetic mouse vessel culture. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormone signaling can change whether a copper-dependent enzyme receives its metal. organism: Mouse tissue_or_cell_type: Aortas, mesenteric vessels and vascular smooth muscle experimental_model: Genetic and streptozotocin diabetes mouse models with vascular rescue assays limitations: Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect. exposure: Diabetes, Atp7a overexpression, copper or insulin ex vivo evidence_span: {"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"} [copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/12538877.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283", "start_char": 0, "end_char": 1579, "text_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283"}

experimental_model

Atox1-null and control immortalized embryonic fibroblasts

exposure

Atox1 deletion and copper challenge

limitations

Trafficking and efflux are related but distinguishable; this is a cell knockout study, not human dietary depletion.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

The copper courier affects transporter behavior as well as total copper content.

primary_references

[copper-p12538877] Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. (2003). https://pubmed.ncbi.nlm.nih.gov/12538877/ DOI: 10.1073/pnas.0336230100

tissue_or_cell_type

Fibroblast Golgi and cellular copper pools

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 377–388

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atox1-null and control immortalized embryonic fibroblasts · source_derived_draft · unverified_draft

### copper-atox1-atp7a-traffic Atox1 loss impaired copper-responsive ATP7A movement from the Golgi even when intracellular copper concentrations were matched. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper courier affects transporter behavior as well as total copper content. organism: Mouse tissue_or_cell_type: Fibroblast Golgi and cellular copper pools experimental_model: Atox1-null and control immortalized embryonic fibroblasts limitations: Trafficking and efflux are related but distinguishable; this is a cell knockout study, not human dietary depletion. exposure: Atox1 deletion and copper challenge evidence_span: {"source_cache": "artifacts/copper-research/12538877.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283", "start_char": 0, "end_char": 1579, "text_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283"} [copper-p12538877] Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. (2003). https://pubmed.ncbi.nlm.nih.gov/12538877/ DOI: 10.1073/pnas.0336230100

evidence_span

{"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"}

experimental_model

Copper-deficient mouse models and subcutaneous copper administration

exposure

Systemic copper depletion and restoration

limitations

Opposite tissue responses are reported regulatory context, not a contradiction in the source.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

The intestine responded in the opposite direction, consistent with delivering copper to the rest of the body.

primary_references

[copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z

tissue_or_cell_type

Intestine, heart, spleen and liver

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 507–518

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper-deficient mouse models and subcutaneous copper administration · source_derived_draft · unverified_draft

### copper-atp7a-intestinal-response Low systemic copper increased intestinal ATP7A, while subcutaneous copper lowered it in the same mouse study. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestine responded in the opposite direction, consistent with delivering copper to the rest of the body. organism: Mouse tissue_or_cell_type: Intestine, heart, spleen and liver experimental_model: Copper-deficient mouse models and subcutaneous copper administration limitations: Opposite tissue responses are reported regulatory context, not a contradiction in the source. exposure: Systemic copper depletion and restoration evidence_span: {"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"} [copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z

evidence_span

{"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"}

experimental_model

Copper-deficient mouse models and subcutaneous copper administration

exposure

Systemic copper depletion and restoration

limitations

Opposite tissue responses are reported regulatory context, not a contradiction in the source.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

Tissues adjusted their copper-export machinery as supply changed.

primary_references

[copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z

tissue_or_cell_type

Intestine, heart, spleen and liver

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 494–505

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper-deficient mouse models and subcutaneous copper administration · source_derived_draft · unverified_draft

### copper-atp7a-peripheral-response Copper deficiency lowered ATP7A abundance in mouse peripheral tissues; subcutaneous copper restored it. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Tissues adjusted their copper-export machinery as supply changed. organism: Mouse tissue_or_cell_type: Intestine, heart, spleen and liver experimental_model: Copper-deficient mouse models and subcutaneous copper administration limitations: Opposite tissue responses are reported regulatory context, not a contradiction in the source. exposure: Systemic copper depletion and restoration evidence_span: {"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"} [copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z

evidence_span

{"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"}

experimental_model

Mouse melanocyte localization and tyrosinase metallation experiments

exposure

ATP7A/BLOC-1-dependent localization

limitations

Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Mouse

plain_language

A trafficking complex directs the copper pump to the pigment compartment.

primary_references

[copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163

tissue_or_cell_type

Golgi and melanosomes

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1001–1012

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse melanocyte localization and tyrosinase metallation experiments · source_derived_draft · unverified_draft

### copper-bloc1-atp7a-location ATP7A localization to melanosomes depended on BLOC-1 in mouse melanocytes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A trafficking complex directs the copper pump to the pigment compartment. organism: Mouse tissue_or_cell_type: Golgi and melanosomes experimental_model: Mouse melanocyte localization and tyrosinase metallation experiments limitations: Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency. exposure: ATP7A/BLOC-1-dependent localization evidence_span: {"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"} [copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163

availability_state

machinery_impairment Imported condition classification; unverified.

curation_topic

copper · Copper

experimental_condition

Control; ATP7A overexpression tested as rescue Akt2 loss · Mouse Akt2-null genotype Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "Akt2 loss", "comparator": "Control; ATP7A overexpression tested as rescue", "endpoint": "SOD3 activity", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "mouse-akt2-null", "state": "Akt2 loss"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Mouse Akt2-null vascular experiments; primary abstract reviewed

limitations

Genetic signaling defect, not dietary copper deficiency. Mechanistic phosphorylation experiments are not substituted for human causal evidence.

primary_references

Sudhahar et al. 2018; DOI:10.1161/ATVBAHA.117.309819; PMID:29301787; https://pubmed.ncbi.nlm.nih.gov/29301787/

trigger_kind

machinery_impairment Imported condition classification; unverified.

Diabetes cascade: targeted primary-source supplement · lines 42–42

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Mouse Akt2-null vascular experiments; primary abstract reviewed · source_derived_draft · unverified_draft

Akt2-null vessels or vascular smooth-muscle cells had lower SOD3 activity, rescued by ATP7A overexpression. Model: Mouse Akt2-null vascular experiments; primary abstract reviewed. Limits: Genetic signaling defect, not dietary copper deficiency. Mechanistic phosphorylation experiments are not substituted for human causal evidence. Primary reference: Sudhahar et al. 2018; DOI:10.1161/ATVBAHA.117.309819; PMID:29301787; https://pubmed.ncbi.nlm.nih.gov/29301787/