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Phenotypes Associated with This Genotype
Genotype
MGI:2659090
Allelic
Composition
Dhhtm1Amc/Dhhtm1Amc
Genetic
Background
involves: 129S1/Sv * C57BL/6J * Swiss Webster
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dhhtm1Amc mutation (1 available); any Dhh mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• in newborn (1-day-old) mice, germ cells were largely present within the seminiferous cords, but many were also found outside the cords
• no synaptonemal complexes were noted in extracordal germ cells, indicating that meiotic development had not occurred
• by 8 days of age, nearly all extracordal germ cells had been lost
• spermatogonia were evident but only a few spermatocytes were observed in masculinized adult males
• rare spermatocytes were observed in feminized adult males
• rare spermatogonia were observed in feminized adult males

endocrine/exocrine glands
• feminized males show numerous layers of fibroblast-like cells with abundant intervening collagen external to the seminiferous tubules
• the fibrosis produced by the accumulation of collagen fibers in the interstitium of feminized testes increased with age
• irregular and anastomotic tubules were observed in feminized adult males; tubular profiles were not rounded and the intertubular tissue displayed a few Leydig cells but extensive fibroblastic tissue
• relatively normal tubule appearance in masculinized adult males with small Sertoli cells and abundant adult-type Leydig cells in the interstitial lymphatic space
• masculinized adult males exhibited adult-type Leydig cells characterized by a dense cytoplasmic matrix, abundant smooth endoplasmic reticulum (SER), whorled ER, and a relative scarcity of lipid and glycogen, as well as an incomplete layer of parietal lymphatic endothelial cells external to the myoid cell layer
• in contrast, feminized males lacked both adult-type Leydig cells and a complete layer of parietal lymphatic endothelial cells; a few clusters of fetal-type Leydig cells were observed, with relatively less SER, a less dense cytoplasmic matrix compared to adult-type Leydig cells, no whorled SER, and abundant lipid and glycoge
• significant reduction or near absence of adult-type Leydig cells in the interstitial testicular region of feminized males
• the relatively few Leydig cells that were present were identified as fetal based on their distinct morphology
• abundance of adult-type Leydig cells in the interstitial lymphatic space of masculinized males
• feminized males displayed immature myoid cells that were abnormally thickened instead of being flattened and lacked organized actin filaments and the pinocytotic vesicles observed in control testes
• in some cases, the myoid cell layer around the seminiferous tubules was discontinuous, with only collagen in the place of absent cells
• in some regions of feminized testes, the basement membrane between the myoid cell and cells of the seminiferous tubules was absent, whereas in other regions, the myoid cells gave rise to numerous microvilli that impinged upon the Sertoli cells
• at 20 days of age, no myoid cells or parietal lymphatic cells could be identified in feminized males
• in some cases where the basement membrane was absent, there was a direct intermingling of Leydig cells with Sertoli cells without any intervening peritubular tissue or extracellular basal laminae
• in masculinized males, Sertoli cells were small and lacked a normal architecture in the relative absence of germ cells
• in feminized males, absence of a basement membrane resulted in apolar Sertoli cells
• the basal lamina of seminiferous cords was not always continuous in newborn and adult mutant mice
• extremely reduced size of testes in both masculinized and feminized males
• testes of masculinized males were larger than those of feminized males
• the mean paired testis weight of feminized males was reduced to only 5% of that in heterozygous control mice
• mutant testes were embedded in the fat pads in proximity to the kidneys

homeostasis/metabolism
• reduced levels of circulating testosterone in feminized males relative to controls (1.39 0.05 ng/ml vs 3.6 0.64 ng/ml, respectively)
• increased levels of circulating LH in feminized males relative to controls (14.1 2.5 ng/ml vs 4.9 1.0 ng/ml, respectively)
• normal serum levels of follicle stimulating hormone (FSH) in feminizied males relative to controls

reproductive system
• in newborn (1-day-old) mice, germ cells were largely present within the seminiferous cords, but many were also found outside the cords
• no synaptonemal complexes were noted in extracordal germ cells, indicating that meiotic development had not occurred
• by 8 days of age, nearly all extracordal germ cells had been lost
• rare spermatogonia were observed in feminized adult males
• masculinized males displayed a relatively longer urogenital-anal distance than feminized males
• feminized males show numerous layers of fibroblast-like cells with abundant intervening collagen external to the seminiferous tubules
• the fibrosis produced by the accumulation of collagen fibers in the interstitium of feminized testes increased with age
• irregular and anastomotic tubules were observed in feminized adult males; tubular profiles were not rounded and the intertubular tissue displayed a few Leydig cells but extensive fibroblastic tissue
• relatively normal tubule appearance in masculinized adult males with small Sertoli cells and abundant adult-type Leydig cells in the interstitial lymphatic space
• masculinized adult males exhibited adult-type Leydig cells characterized by a dense cytoplasmic matrix, abundant smooth endoplasmic reticulum (SER), whorled ER, and a relative scarcity of lipid and glycogen, as well as an incomplete layer of parietal lymphatic endothelial cells external to the myoid cell layer
• in contrast, feminized males lacked both adult-type Leydig cells and a complete layer of parietal lymphatic endothelial cells; a few clusters of fetal-type Leydig cells were observed, with relatively less SER, a less dense cytoplasmic matrix compared to adult-type Leydig cells, no whorled SER, and abundant lipid and glycoge
• significant reduction or near absence of adult-type Leydig cells in the interstitial testicular region of feminized males
• the relatively few Leydig cells that were present were identified as fetal based on their distinct morphology
• abundance of adult-type Leydig cells in the interstitial lymphatic space of masculinized males
• feminized males displayed immature myoid cells that were abnormally thickened instead of being flattened and lacked organized actin filaments and the pinocytotic vesicles observed in control testes
• in some cases, the myoid cell layer around the seminiferous tubules was discontinuous, with only collagen in the place of absent cells
• in some regions of feminized testes, the basement membrane between the myoid cell and cells of the seminiferous tubules was absent, whereas in other regions, the myoid cells gave rise to numerous microvilli that impinged upon the Sertoli cells
• at 20 days of age, no myoid cells or parietal lymphatic cells could be identified in feminized males
• in some cases where the basement membrane was absent, there was a direct intermingling of Leydig cells with Sertoli cells without any intervening peritubular tissue or extracellular basal laminae
• in masculinized males, Sertoli cells were small and lacked a normal architecture in the relative absence of germ cells
• in feminized males, absence of a basement membrane resulted in apolar Sertoli cells
• the basal lamina of seminiferous cords was not always continuous in newborn and adult mutant mice
• extremely reduced size of testes in both masculinized and feminized males
• testes of masculinized males were larger than those of feminized males
• the mean paired testis weight of feminized males was reduced to only 5% of that in heterozygous control mice
• mutant testes were embedded in the fat pads in proximity to the kidneys
• both masculinized (7.5%) and feminized (92.5%) males showed abnormal peritubular tissue and severely depressed spermatogenesis
• spermatogonia were evident but only a few spermatocytes were observed in masculinized adult males
• rare spermatocytes were observed in feminized adult males
• 92.5% of mutant males were pseudohermaphrodites with an external female phenotype, evidence of mammary teats, and a blind vaginal opening; the remaining 7.5% mutant males were masculinized
• penetrance within the 92.5% varied; for example, some males were only partly feminized with colored teat hairs but lacking a blind vaginal opening
• internally, masculinized males were similar to feminized males except that the overall size of the reproductive tract was relatively larger, although still smaller, than that of wild-type or heterozygous controls

digestive/alimentary system
• masculinized males displayed a relatively longer urogenital-anal distance than feminized males

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
46,XY sex reversal DOID:14448 OMIM:607080
OMIM:PS400044
J:65900


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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last database update
02/23/2021
MGI 6.16
The Jackson Laboratory