Abstract
Kallmann syndrome is a form of hypogonadotropic hypogonadism also associated with the loss of smell. It is a phenotypically and genetically heterogeneous disorder, with mutations in several known causative genes now accounting for approximately 30% of cases. The prevalence for the disease is also much higher in males than in females, a phenomenon that remains to be fully explained. Here, we show that loss of Prokr2, which is linked to autosomal recessive Kallmann syndrome type 3 ( KAL3; OMIM 244200), affects fetal testis differentiation in mice. We find that Prokr2 is specifically expressed in the XY gonads during sex determination and fetal sexual differentiation, and knockout mice display a variable degree of compromised vasculature in the fetal testes. This phenotype offers potential insight into the clinical heterogeneity observed within familial cases, and may contribute to the gender bias in Kallmann syndrome patients. Copyright (C) 2012 S. Karger AG, Basel
| Original language | English |
|---|---|
| Journal | Sexual Development |
| Volume | 5 |
| Issue number | 6 |
| Pages (from-to) | 294-303 |
| Number of pages | 10 |
| ISSN | 1661-5425 |
| DOIs | |
| Publication status | Published - 2011 |
| Externally published | Yes |
Keywords
- Animals
- Female
- Gonads
- Immunohistochemistry
- Kallmann Syndrome
- Male
- Mice
- Mice, Knockout
- Real-Time Polymerase Chain Reaction
- Receptors, G-Protein-Coupled
- Receptors, Peptide
- Sex Differentiation
- Testis
- Prokr2 protein, mouse
- Mus
- G protein coupled receptor
- receptor
- animal
- article
- cytology
- female
- genetics
- gonad
- immunohistochemistry
- Kallmann syndrome
- male
- metabolism
- mouse
- mouse mutant
- pathology
- physiology
- prenatal development
- real time polymerase chain reaction
- sex differentiation
- testis
- Disorder of sexual development
- Gonadogenesis
- Mouse model
- Sex determination
- Vasculogenesis
- cell differentiation
- clinical heterogeneity
- OMIM 244200
- sex determination
- sexual differentiation
- vasculature dysmorphology
- Kallmann syndrome type 3 KAL3 congenital disease, endocrine disease/gonads, reproductive system disease, genetic disease etiology, genetics
- Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae [86375] mouse common embryo, fetus female, male strain-CD1, strain-Jcl:ICR
- mouse Amh gene [Muridae]
- mouse Cdh5 gene [Muridae]
- mouse Ddx4 gene [Muridae]
- mouse Efnb2 gene [Muridae]
- mouse Ephb2 gene [Muridae]
- mouse Hes1 gene [Muridae]
- mouse Hey1 gene [Muridae]
- mouse Hsd3b1 gene [Muridae]
- mouse Notch1 gene [Muridae]
- mouse Notch2 gene [Muridae]
- mouse Notch3 gene [Muridae]
- mouse Nr5a1 gene [Muridae]
- mouse Pecam1 gene [Muridae]
- mouse Prokr2 gene [Muridae] expression, loss of function mutation
- mouse Rps29 gene [Muridae]
- mouse Sdha gene [Muridae]
- 03502, Genetics - General
- 03506, Genetics - Animal
- 16504, Reproductive system - Physiology and biochemistry
- 16506, Reproductive system - Pathology
- 17002, Endocrine - General
- 17006, Endocrine - Gonads and placenta
- 25502, Development and Embryology - General and descriptive
- 25503, Development and Embryology - Pathology
- Biochemistry and Molecular Biophysics
- Chemical Coordination and Homeostasis
- Reproduction
- gonad reproductive system, endocrine system
- testis reproductive system
- Endocrine System
- Genetics
- Molecular Genetics
- Reproductive System
- DEVELOPMENTAL
- GENES-ENCODING PROKINETICIN-2
- MAMMALIAN SEX DETERMINATION
- HORMONE-RELEASING HORMONE
- ENDOTHELIAL GROWTH-FACTOR
- OF-FUNCTION MUTATIONS
- RT-PCR ANALYSIS
- HYPOGONADOTROPIC HYPOGONADISM
- OLFACTORY PLACODE
- CELLS
- MOUSE