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#sex reversal

2 public questions tagged with this topic.

Sex determination-l

Which gene mutation can cause XX mammals to develop testes?

Dataset key indicates mutation causing XX mammals to develop testes listed is Rspo1, illustrating ovary-maintenance failure leading to masculinization. Classically XX sex reversal with complete testes also arises from Sox9 enhancer duplication or gain-of-function rearrangements upregulating Sox9 independent of Sry, or from FOXL2 loss. However provided options highlight Rspo1 loss which eliminates Wnt4/β-catenin reinforcement, permitting Sox9/Fgf9 male program to dominate even without Sry. Such XX individuals develop testes, male internal ducts and external masculinization despite absence of Y, recapitulating human RSPO1-related disorder of sex development.

Ref: Nature Genetics, RSPO1 loss causes XX testes; Gilbert Chapter 6: Genes causing XX sex reversal.

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sex determination-ll

Sex reversal mutations in mammals occur in:

Sex reversal in mammals can occur through mutations in multiple genes because gonadal fate depends on balanced antagonistic loops. Loss of ovary-promoting genes Wnt4, Rspo1, Foxl2 or β-catenin derepresses Sox9 leading to XX testes, while duplication or enhancer activation of Sox9 itself also causes XX sex reversal. Conversely loss of Sox9, Sf1 or Fgf9 causes XY male-to-female reversal with ovaries. Mutations affecting β-catenin stabilization produce similar phenotypes. Since testis and ovary programs mutually inhibit each other, disrupting any node can tilt balance, therefore correct answer includes all listed genes as capable of causing reversal.

Ref: Nature Reviews Genetics, Disorders of Sex Development - antagonistic pathway mutations causing sex reversal.

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